Posted on 11/10/2021 by Melbourne Blood Specialiss
3rd vaccine dose

ATAGI recommendations

  • ATAGI recommends a 3rd dose of COVID-19 vaccine as part of the primary course in individuals who are severely immunocompromised.
  • This is to address the risk of suboptimal or non-response to the standard 2 dose schedule.  
  • The 3rd dose is intended to maximise the level of immune response to as close as possible to the general population.
  • This recommendation applies to all individuals aged ≥12 years with certain conditions or on therapies leading to severe immunocompromise, as defined in Box 1.
  • An individual with an unlisted condition should only be considered for a 3rd dose where the treating physician has assessed the patient as having a similar level of severe immunocompromise to the listed conditions in Box 1, and where the benefits of a 3rd dose of COVID-19 vaccine outweigh the risks.
  • Individuals who currently are not severely immunocompromised but who will commence significant immunosuppressive therapy ≥ 2 weeks after their 2nd dose do not require a 3rd dose, as it can be expected that an adequate response to 2 primary doses will be achieved.
  • ATAGI does not recommend subsequent doses beyond the 3rd dose at this time. Many patients who fail to respond to 3rd doses may not respond to further doses.
  • Protection from 3 primary doses in severely immunocompromised individuals may still be lower than the general population. People should continue risk mitigation strategies such as mask wearing and social distancing even after receipt of a 3rd dose.
  • ATAGI will continue to monitor the evidence around duration of protection and advise on the need for subsequent (booster) doses in immunocompromised populations to address waning of protection or risk from variants of concern.
  • ATAGI will provide further advice on booster doses (including for healthcare workers, older adults and the general population) separately. See about the need for additional doses of COVID-19 vaccines.

Recommendations specific to the 3rd dose

  • An mRNA vaccine (Pfizer or Moderna) is preferred to Vaxzevria (AstraZeneca) for this 3rd dose.
  • AstraZeneca can be used for the 3rd dose for individuals who have received AstraZeneca for their first 2 doses if there are no contraindications or precautions for use, or if a significant adverse reaction has occurred after a previous mRNA vaccine dose which contraindicates further doses of mRNA vaccine (e.g., anaphylaxis, myocarditis).
  • The recommended interval for the 3rd dose is 2 to 6 months after the 2nd dose of vaccine. A minimum interval of 4 weeks may be considered in exceptional circumstances (e.g., anticipated intensification of immunosuppression, outbreaks). People who have had a second dose more than 6 months ago should receive a 3rd dose whenever feasible.

These recommendations have been prepared in consultation with the Australasian Society of Clinical Immunology and Allergy (ASCIA).

Antibody testing is not recommended to assess for immunity to SARS-CoV-2 following COVID-19 vaccination, including in immunocompromised individuals after a 2nd or 3rd dose. There are no serological assays that provide a definitive correlate of immunity to SARS-CoV-2. Further information on these recommendations is available in the ATAGI Recommendations on the use of a 3rd primary dose of COVID-19 vaccine in individuals who are severely immunocompromised.

Box 1: People with the following immunocompromising conditions and therapies for which a 3rd primary dose is recommended

  • Active haematological malignancy
  • Non-haematological malignancy with current active treatment including chemotherapy, radiotherapy, and/or hormonal therapy, but excluding immunotherapy with immune checkpoint inhibitors
  • Solid organ transplant with immunosuppressive therapy
  • Haematopoietic stem cell transplant (HSCT) recipients or chimeric antigen receptor T-cell (CAR-T) therapy within 2 years of transplantation.

    • These patients require revaccination with 3 additional doses of COVID-19 vaccine, irrespective of doses given prior to transplantation, commencing generally ≥3-6 months after their transplant after discussion with their treating specialist.

    • Those beyond 2 years from transplant should discuss with their treating specialist about the need for a 3rd dose.
  • Immunosuppressive therapies including:

    • High dose corticosteroid treatment equivalent to >20mg/day of prednisone for ≥14 days in a month, or pulse corticosteroid therapy.

    • Multiple immunosuppressants where the cumulative effect is considered to be severely immunosuppressive.
    • Selected conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDS):

      • including mycophenolate, methotrexate (>0.4 mg/kg/week), leflunomide, azathioprine (>3mg/kg/day), 6-mercaptopurine (>1.5 mg/kg/day), alkylating agents (e.g. cyclophosphamide, chlorambucil), and systemic calcineurin inhibitors (e.g. cyclosporin, tacrolimus)

      • excluding hydroxychloroquine or sulfasalazine when used as monotherapy
    • Biologic and targeted therapies anticipated to reduce the immune response to COVID-19 vaccine:

      • including B cell depleting agents (e.g. anti-CD20 monoclonal antibodies, BTK inhibitors, fingolimod), anti-CD52 monoclonal antibodies (alemtuzumab), anti-complement antibodies (e.g. eculizumab), anti-thymocyte globulin (ATG) and abatacept

      • excluding agents with likely minimal effect on vaccine response such as immune checkpoint inhibitors, anti-integrins, anti-TNF-α, anti-IL1, anti-IL6, anti-IL17, anti-IL4 and anti-IL23 antibodies
  • Primary immunodeficiency including combined immunodeficiency and syndromes, major antibody deficiency (e.g., common variable immune deficiency (CVID) or agammaglobulinemia), defects of innate immunity (including phagocytic cells), defects of immune regulation, complement deficiencies and phenocopies of primary immunodeficiencies.
  • Advanced or untreated HIV with CD4 counts <250/μL or those with a higher CD4 count unable to be established on effective antiretroviral therapy

    • a 3rd primary dose is not required for people living with HIV, receiving ART with CD4 counts ≥250/μL

  • Long term haemodialysis or peritoneal dialysis
30/09/2021
by Melbourne Blood Specialists

About COVID-19 vaccines

Information about COVID-19 vaccines including side effects, who to contact for medical support, and useful resources about the vaccination process

On this page

COVID-19 vaccines are being used in Victoria

These vaccines have been approved for use in Australia:

| | | | | ------------------- | ---------------------------------------- | ---------------------------------------- | | Vaccine brand | When you should get your second dose | Age groups eligible for this vaccine | | Pfizer vaccine | 6 weeks after your first dose | People aged 12-59 years | | AstraZeneca vaccine | 6 weeks after your first dose | People aged 18 years and older | | Moderna vaccine | 6 weeks after your first dose | People aged 12-59 years |

The Pfizer vaccine is also offered to anyone eligible for a reserved Pfizer appointment, regardless of their age. Read more about who can get vaccinated through reserved appointments.

Pfizer and Moderna are the preferred vaccines for people under the age of 60. People aged 18 - 59 years can choose to get AstraZeneca if they provide verbal consent on the risks, including thrombosis thrombocytopenia (TTS). If you book an AstraZeneca appointment you will receive the AstraZeneca vaccine.

Learn more about:

You will need two doses (injections) of the vaccine. COVID-19 vaccines are much more effective if you get your second dose. Get the same brand of vaccine for each dose.

Vaccines are strictly tested for safety

Before COVID-19 vaccines are used in Australia, they must pass strict safety standards set by Australia’s independent medicines regulator, the Therapeutic Goods Administration

.

The COVID-19 vaccines being used in Australia have been used by hundreds of millions of people around the world. As at 15 September 2021, more than 14 million people across Australia have now received their first dose of this vaccine.

Both vaccines are very effective at preventing infection with COVID-19, and serious illness from COVID-19, including new variants of COVID-19.

COVID-19 vaccines are free, safe and voluntary. Choosing to get vaccinated helps protect ourselves, our families and our community.

Vaccine side effects

Common reactions to COVID-19 vaccinations include:

  • pain where you had the injection
  • tiredness
  • muscle aches
  • headache
  • fever and chills
  • joint pain.

These are expected side effects that are generally mild and on average last a day or two. Serious side effects like allergic reactions or anaphylaxis are extremely rare.

Vaccine ingredients are tested for safety in the manufacturing process.

Your options if you are worried about side effects

  • Talk to your doctor or healthcare provider
  • Call Nurse on Call
  • Call the Australian Government Department of Health COVID-19 Hotline on 1800 020 080 (available 24 hours a day)
  • Call 000 if you have difficulty breathing, a fast heartbeat, are wheezing, or are otherwise seriously unwell.

When to seek medical attention after a vaccination

After your AstraZeneca vaccine, talk to your doctor immediately if:

  • You have an expected side effect of the vaccine that has not gone away after a few days
  • You have any of the following symptoms, particularly between 4 and 42 days after vaccination:

    • A headache that keeps coming back. It might:

      • be mild or strong

      • be present beyond 48 hours after vaccination, or come later than 48 hours after vaccination
      • feel worse when you lie down
      • go away for a little while when you take pain relief like paracetamol, but then it comes back
    • Nausea or vomiting.
    • Blurred vision, difficulty speaking, drowsiness or confusion, or seizures.
    • Abdominal (belly) pain that won’t go away.
    • Shortness of breath or chest pain.
    • Lower limb pain, redness or swelling.
    • Tiny blood spots under the skin away from the area where the injection was received.

View more on thrombosis thrombocytopenia syndrome (TTS) and related symptoms.

After your Pfizer or Moderna vaccine:

Talk to your doctor immediately if:

  • You have an expected side effect of the vaccine which has not gone away after a few days.
  • You feel pain or pressure in your chest.
  • It hurts when you breathe.
  • You find it hard to take deep breaths.
  • You have an irregular heartbeat, skipped beats or ‘fluttering’ feelings in your chest.
  • You faint.

For more on cardiac side effects after COVID-19 vaccination.

Tell your doctor you have recently received the vaccine.

COVID-19 vaccines are created following strong ethical standards

There are strong ethical standards surrounding the use of cells in vaccine development. COVID-19 vaccines meet these standards.

There are no foetal cells in the COVID-19 dose (injection) that you receive.

COVID-19 variants

All viruses evolve over time. This includes SARS-CoV-2, the virus that causes COVID-19.

When a virus spreads through a community, it makes more copies of itself. When the virus makes copies, it sometimes changes a little bit. These changes are called mutations. A virus with one or more new mutations is called a ‘variant’ of the original virus. AstraZeneca Pfizer, and Moderna vaccines are very effective in preventing serious illness or hospitalisation from COVID-19.

Maintain COVIDSafe behaviours

Reducing the spread of COVID-19 helps reduce the number of times the virus copies itself. To do this, we must maintain COVIDSafe settings to help reduce the chance the virus will change into a new variant.

In some cases, the variant acts in a different way compared to the original virus. For example, some new COVID-19 variants appear to be more infectious or cause more severe diseases.

How variants affect COVID-19 vaccines

Even if the virus changes, COVID-19 vaccines still help your body recognise and fight the virus.

After two doses, AstraZeneca, Pfizer and Moderna vaccines all reduce the risk of serious illness and hospitalisation from the Delta variant. It is important to get your second dose of the vaccine to protect against new variants of COVID-19.

The Therapeutic Goods Administration (TGA)

looks closely at variants and their effect on vaccines as part of their approval and monitoring processes.

Variants may mean people need additional or booster shots, like we do for tetanus and whooping cough. It may also mean we need to be vaccinated regularly, like the flu vaccine each year.

How COVID-19 vaccines were developed

There are many reasons why COVID-19 vaccines were able to be developed quickly and safely.

Scientists developing these vaccines had access to a lot of resources.

To develop the COVID-19 vaccine, many people, companies and research facilities offered money, resources, equipment, and teamwork to make the process as efficient as possible because of the seriousness of the global pandemic.

Existing technologies helped researchers develop a COVID-19 vaccine.

COVID-19 vaccines are a new type of vaccine, but the technology used to develop them is not new and has been researched and tested for many years.

Technology made data analysis quicker and easier for scientists researching COVID-19 vaccines.

This can also help scientists research lots of different vaccines at the same time.

Overlapping research and clinical trial phases made the process faster.

In traditional vaccine development, each phase is carried out separately, which takes longer.COVID-19 vaccines were safely manufactured at the same time as clinical trials, which helped make the process quicker. Ensuring a COVID-19 vaccine is safe to use is always the top priority during its development.\ \ Vaccine regulators check all COVID-19 vaccine data as soon as it becomes available (rather than waiting for all data to be ready and checking in one go, like they do for other vaccines). Regulators carry out all the same tests as they do with other vaccines.

The manufacturing process is more efficient.

The manufacturing process begins while a vaccine is going through the approvals process. As soon as a COVID-19 vaccine is approved for use, the vaccines are already made and ready to use.

Useful Australian Government resources

A statement from the Australian Technical Advisory Group on Immunisation (ATAGI) on the AstraZeneca COVID-19 vaccine in response to new vaccine safety concerns.

Summary

The Australian Technical Advisory Group on Immunisation (ATAGI) recommends the COVID-19 Pfizer vaccine (Comirnaty) as the preferred vaccine for those aged 16 to under 60 years. This updates the previous preferential recommendation for Comirnaty over COVID-19 Vaccine AstraZeneca in those aged 16 to under 50 years. The recommendation is revised due to a higher risk and observed severity of thrombosis and thrombocytopenia syndrome (TTS) related to the use of AstraZeneca COVID-19 vaccine observed in Australia in the 50-59 year old age group than reported internationally and initially estimated in Australia.

For those aged 60 years and above, the individual benefits of receiving a COVID-19 vaccine are greater than in younger people. The risks of severe outcomes with COVID-19 increase with age and are particularly high in older unvaccinated individuals. The benefit of vaccination in preventing COVID-19 with COVID-19 Vaccine AstraZeneca outweighs the risk of TTS in this age group and underpins its ongoing use in this age group.

People of any age without contraindications who have had their first dose of COVID-19 Vaccine AstraZeneca without any serious adverse events should receive a second dose of the same vaccine. This is supported by data indicating a substantially lower rate of TTS following a second COVID-19 Vaccine AstraZeneca dose in the United Kingdom (UK).

Background

The Australian COVID-19 vaccination program has the overarching goal of protecting all people in Australia from the harm caused by the novel coronavirus SARS-CoV-2.

On 8 April 2021, ATAGI recommended that Comirnaty was the preferred vaccine for people under the age of 50 years due to local and international reports of thrombosis and thrombocytopenia syndrome (TTS) following COVID-19 Vaccine AstraZeneca.

Based on available international data at that time, the estimated risk of TTS was 4-6 per million cases following a first dose of COVID-19 Vaccine AstraZeneca. Given the ongoing risk of COVID-19 outbreaks, low vaccine coverage, and increasing rate of severe COVID-19 outcomes in older individuals, it was considered that the benefits of COVID-19 Vaccine AstraZeneca outweighed the risk in those over 50 years. As such, no preferential recommendation for either vaccine was made in this age group. This advice was reinforced on 23 April 2021 and has been reviewed weekly by ATAGI since then.

Principles underpinning the revised recommendations

In making the decision to revise the previous recommendation, ATAGI has considered several factors that have been monitored closely, including:

  • The potential risk of severe illness and death from COVID-19 over the coming months
  • Minimising harms to people due to adverse events following immunisation
  • Australian data on the age-specific risks and severity of TTS following COVID-19 Vaccine AstraZeneca
  • The expected vaccine supply over the months ahead
  • The impacts of any change in recommendation on the COVID-19 vaccine program.

The benefits of vaccination to prevent COVID-19

There is an ever-present risk of COVID-19 in Australia while the population remains largely susceptible to infection. Recent events in Victoria have demonstrated how rapidly outbreaks can spread despite intensive contact tracing and public health action. As at 16 June 2021, 63% of people aged 70 years and older and 25% of those aged 18 years and older have received at least one dose of a COVID-19 vaccine.

The risk of severe COVID-19 is strongly related to increasing age. In 2020, for every 100 people with COVID-19 aged between 50-59 years, around 14 were hospitalised and 3 required admission to an intensive care unit (ICU). One in every 600 people with COVID-19 in this age group died. In contrast, for every 100 people aged 70-79 years with COVID-19, around 38 were hospitalised, 7 were admitted to ICU and 4 died (ie. 24 deaths in 600). Therefore, the benefit of vaccination in preventing COVID-19 is greater in older people. If an outbreak occurred comparable to the first wave in Australia, the benefits in preventing severe COVID-19 would outweigh the risks of TTS due to COVID-19 Vaccine AstraZeneca in older adults, as illustrated in Weighing up the potential benefits against the risk of harm from COVID-19 Vaccine AstraZeneca.

ATAGI acknowledges the difficulty in balancing the small risk of a clinically significant adverse event related to vaccination with COVID-19 Vaccine AstraZeneca against the need to protect individuals and the community against the ongoing threat of COVID-19, together with ongoing limitations and uncertainties about the supply of alternative COVID-19 vaccines. ATAGI emphasises that this advice is specific to the context that there is currently no or limited community transmission in most of Australia and would be different in other countries.

The risks of TTS after COVID-19 Vaccine AstraZeneca

From early April to 16 June 2021, 60 cases of confirmed or probable TTS have been reported in Australia. This includes an additional seven cases reported in the past week in people between 50-59 years, increasing the rate in this age group from 1.9 to 2.7 per 100,000 AstraZeneca vaccine doses. The revised estimates of risk associated with first doses of COVID-19 Vaccine AstraZeneca are listed in the table below.

TTS is a serious condition in a proportion of individuals who develop it. The overall case fatality rate in Australia (3%; 2 deaths among 60 cases) is lower than has been reported internationally. This is likely to reflect increased detection due to heightened awareness, as well as early diagnosis and treatment. A spectrum of severity of illness has been reported in Australia, from fatal cases and those with significant morbidity, to relatively milder cases. TTS appears to be more severe in younger people.

There are different ways in which the severity of TTS can be measured. The US Centers for Disease Control and Prevention (CDC) defines “tier 1” cases as clots involving unusual sites, such as the veins of the brain (cerebral venous sinus thrombosis) or abdomen (splanchnic thrombosis); these are generally more severe and may potentially lead to long term health complications. In those under 60 years, 52% of TTS episodes are occurring in tier 1 sites compared with 28% in those 60 years and older. Other markers of severity include the requirement for intensive care (33% of TTS in those under 60 years; 15% of TTS cases in those 60 years and older), and fatal cases (both occurring in those < 60 years).

Second dose recommendations for COVID-19 Vaccine AstraZeneca

ATAGI supports completion of a two-dose schedule with COVID-19 Vaccine AstraZeneca, based on current evidence. The risk of TTS following a second dose of COVID-19 Vaccine AstraZeneca is much lower than the risk following a first dose. The UK has reported 23 TTS cases in 15.7 million people after receiving a second dose, an estimated rate of 1.5 per million second doses (compared to a reported risk of 14.2 per million first doses in the UK).

People of any age without contraindications who have had their first dose of COVID-19 Vaccine AstraZeneca without any serious adverse events should receive the second dose.

Recommendations

  • ATAGI advises that Comirnaty is preferred over COVID-19 Vaccine AstraZeneca from the age of 16 to under 60 years. This is based on recent data regarding TTS cases in Australia and a reassessment of current age-specific risks and benefits of vaccination.
  • ATAGI considers the benefit of vaccination in preventing COVID-19 with COVID-19 Vaccine AstraZeneca outweighs the risk of TTS in people aged 60 and above. For this age group, the benefits of receiving a COVID-19 vaccine are greater than in younger people. The risks of severe outcomes with COVID-19 increase with age and are particularly high in older unvaccinated individuals.
  • COVID-19 Vaccine AstraZeneca can be used in adults aged under 60 years for whom Comirnaty is not available, the benefits are likely to outweigh the risks for that individual and the person has made an informed decision based on an understanding of the risks and benefits.
  • People of any age without contraindications who have had their first dose of COVID-19 Vaccine AstraZeneca without any serious adverse events should receive the second dose.
  • ATAGI reinforces the importance of providing clear communications to people who have received or are considering COVID-19 Vaccine AstraZeneca, and notes guidance documents for consumers, for primary care and for hospitals are being continually revised to accommodate this new recommendation.

A joint statement from the Australian Technical Advisory Group on Immunisation (ATAGI) and the Thrombosis and Haemostasis society of Australia and New Zealand (THANZ) on Thrombosis with Thrombocytopenia Syndrome (TTS) and the use of COVID-19 Vaccine AstraZeneca.

Key points

  • TTS, also known as vaccine induced thrombotic thrombocytopenia (VITT), is a rare newly identified condition with a different mechanism to other causes of thrombosis. Among case reports, there are no known markers for increased risk for TTS/VITT.
  • The risk of TTS is not likely to be increased in people with the following conditions, and people in these groups can receive COVID-19 Vaccine AstraZeneca:
    • History of blood clots in typical sites
    • Increased clotting tendency that is not immune mediated
    • Family history of blood clots
    • History of ischaemic heart disease or stroke
    • Current or past thrombocytopenia (low platelet count)
    • Those receiving anticoagulation therapy
  • The list of conditions for which Comirnaty (Pfizer) is the preferred vaccine has been expanded to also include:
    • Past history of idiopathic splanchnic (mesenteric, portal, splenic) vein thrombosis
    • Antiphospholipid syndrome with thrombosis
  • TTS can be treated effectively. Guidance on the identification and management of TTS is available from the Thrombosis and Haemostasis Society of Australia and New Zealand.

Statement

The Australian Technical Advisory Group on Immunisation (ATAGI) and the Thrombosis and Haemostasis Society of Australia and New Zealand (THANZ) are closely monitoring local and international data on the very rare and newly identified condition associated with COVID-19 Vaccine AstraZeneca called thrombosis with thrombocytopenia syndrome (TTS) or vaccine induced thrombotic thrombocytopenia (VITT).

This joint statement provides updated information about TTS and reinforces ATAGI’s previous advice regarding the use of COVID-19 Vaccine AstraZeneca.

TTS is distinct from other clotting conditions

TTS is different from other blood clotting conditions and is triggered by the immune system’s response to the COVID-19 Vaccine AstraZeneca. It results in both thrombosis and low platelet levels. In the majority of cases, pathological antibodies against platelet factor 4 (PF4), a protein released from platelets, are detected. Studies are ongoing to better understand the exact mechanism of TTS. TTS has been reported in patients who have received the COVID-19 Vaccine AstraZeneca and the Janssen COVID-19 Vaccine (the latter is not used in Australia).

TTS is a rare condition with a different mechanism to most other causes of thrombosis and/or thrombocytopenia. Among case reports, there are no known markers for increased risk for TTS.

Based upon this, the following groups of people can receive COVID-19 Vaccine AstraZeneca:

  • People with a past history of venous thromboembolism in typical sites, such as deep vein thrombosis or pulmonary embolism
  • People with a predisposition to form blood clots, such as those with Factor V Leiden, or other non-immune thrombophilic disorders
  • People with a family history of clots or clotting conditions
  • People currently receiving anticoagulant medications
  • People with a history of ischaemic heart disease or cerebrovascular accident
  • People with a current or past history of thrombocytopenia.

TTS can now be treated very effectively. THANZ have developed guidance on identification and treatment of TTS.

As part of informed consent for each dose, people who are considering being vaccinated with COVID-19 Vaccine AstraZeneca should be aware that TTS is a very rare potential complication. They should be advised of the possible symptoms of TTS and when to seek medical advice.

Comirnaty (Pfizer), the alternative COVID-19 vaccine available in Australia, is the preferred vaccine brand for:

  • People aged under 50 years, since the risk of TTS, albeit very low, appears to be higher in younger adults.

Comirnaty (Pfizer) is recommended for people 16 years and above with:

  • A past history of cerebral venous sinus thrombosis (CVST)
  • A past history of heparin-induced thrombocytopenia (HIT)
  • A past history of idiopathic splanchnic (mesenteric, portal and splenic) venous thrombosis
  • Anti-phospholipid syndrome with thrombosis
  • People with contraindications to COVID-19 Vaccine AstraZeneca, i.e.
    • Anaphylaxis to a previous dose of COVID-19 Vaccine AstraZeneca, or to an ingredient of the vaccine
    • Thrombosis with thrombocytopenia occurring after the first dose of COVID-19 Vaccine AstraZeneca
    • Other serious adverse events attributed to the first dose of COVID-19 Vaccine AstraZeneca

The risk of TTS is lower after the second dose

UK data suggests that the risk of TTS is much lower with a second dose, with 15 cases reported to date out of 9.0 million second doses of COVID-19 Vaccine AstraZeneca given. This translates into an estimated rate of 1.7 case per million doses.

ATAGI reinforces that people of any age who have had their first dose of COVID-19 Vaccine AstraZeneca without any serious adverse events can receive the second dose.

Benefits of vaccination

Vaccination against COVID-19 remains the best way to prevent severe illness and death from COVID-19. The benefits of vaccination are many and include protection against severe illness and death from COVID-19 for the individual, as well as indirect benefits for the community. The risk of potential outbreaks of COVID-19 is ever-present. The Australian population remains largely unimmunised and susceptible to COVID-19 risks.

People who choose to delay vaccination until a vaccine other than AstraZeneca COVID-19 vaccine is available should be aware they may not be protected against COVID-19 for months. ATAGI and THANZ acknowledge the challenges of decision making as information continues to emerge.

Weekly updates are provided by the Therapeutic Goods Administration (TGA) on TTS in Australia, and ATAGI on rates of TTS by age and any related updates to recommendations on COVID-19 vaccine use. To keep up to date visit health.gov.au/news.

05/05/2021
by Prof Con Tam & A/Prof Ali Bazargan

Vaccines rolled out in Australia are Pfizer and AstraZeneca. Before vaccines are made available in Australia they need to pass strict Australian safety standards and tests set by the Therapeutic Goods Administration (TGA).

The most prioritised groups in the community (ie. staff in involved in the vaccination program, hotel quarantine staff, airport staff etc.) have largely been immunised now together with immunosuppressed/cancer patients.

Most of our patients are expected to be vaccinated from May onwards.

AstraZeneca is not currently recommended for individuals less than 50 years of age and those people will receive the Pfizer vaccine when available. Some patients with cancer who are under 50 years of age are at particularly high risk of death with COVID and, in these cases, we may recommend the AstraZeneca vaccine over waiting for Pfizer.

Community roll out is well under way through GP clinics, designated hospitals & mass vaccination centres. Up-to-date information can be obtained from the Dept Health & Human Services website: coronavirus.vic.gov.au/vaccine

Phone for a vaccination appointment on 1800 675 398.

All of the vaccines work and are safe for immunocompromised patients and people who have had a DVT or PE in the past. We strongly recommend patients and their families take the first opportunity to receive the vaccine. The best vaccine is the first one available to you.

30/04/2021
by A/Prof Ali Bazargan

Following the Australian Technical Advisory Group on Immunisation (ATAGI) statement of 19 March 2021 on the safety of the AstraZeneca COVID-19 vaccine, ATAGI notes that the World Health Organization (WHO) and regulatory agencies including the European Medicines Agency (EMA) and the Australian Therapeutic Goods Administration (TGA) have been reviewing data from tens of millions of people given the AstraZeneca and other COVID-19 vaccines worldwide.

This shows that there is no increase in the rates of general thromboembolic disorders after vaccination over expected rates, noting these conditions occur commonly in the absence of vaccination.

The EMA and others have also been conducting ongoing investigations in Europe regarding reports of a specific type of thrombosis (cerebral venous sinus thrombosis; CVST) following AstraZeneca vaccine.

It is not known whether this condition is linked to vaccination. Cases of CVST reported overseas have mostly occurred 4 to 14 days following the AstraZeneca vaccine and have been rare (varying reports of 1 to 8 per million doses of vaccine given). Further studies in these patients are ongoing to understand if there is a potential link with vaccination. No cases of CVST associated with vaccination have been recorded in Australia to date.

Overall, ATAGI emphasises that the benefits of the COVID-19 vaccine far outweigh this potential risk. Based on this information, ATAGI considers that there is no evidence of a risk of thrombotic disease after COVID-19 vaccination in people with a history of clotting conditions. ATAGI continues to recommend vaccination with either AstraZeneca or Pfizer (Comirnaty) COVID-19 in such people. This includes those with deep venous thrombosis and/or pulmonary embolism; people with risk factors for thrombosis (such as use of oral contraceptives or smoking); people with thrombocytopenia (low platelets that can occur with clotting conditions); people with known thrombophilic disorders; people on anticoagulants (e.g. warfarin) and people with a history of cardiovascular disease (such as myocardial infarction or stroke).

However, for the time being, ATAGI recommends that vaccination with any COVID-19 vaccine should be deferred for people who have a history of the following rare conditions. This is until further information from ongoing investigations in Europe is available and is only a precautionary measure:

  1. people with a confirmed medical history of CVST and/or

  2. people with a confirmed medical history of heparin induced thrombocytopenia (HIT). HIT is an immune-mediated complication of treatment with heparin that affects platelet function. A HIT- like mechanism is being investigated as a potential, but unconfirmed, pathway to CVST post COVID-19 vaccination.

As for all vaccines, including COVID-19 vaccines, patients and health care providers should be alert for persistent, unexpected and/or severe adverse events following immunisation, particularly those that occur 1–2 weeks after vaccination.

ATAGI encourages health care providers and the public to report any unexpected or serious adverse events occurring following any COVID-19 vaccines. These should be appropriately investigated and further advice sought from specialist services.

Mantle Cell Lymphoma (MCL) is one of the more uncommon types of blood cancers and accounts only for 5-10% of all types of Non-Hodgkin Lymphomas. MCL is an incurable type of Lymphoma. However, it differs from other types of incurable Lymphomas as it grows relatively quickly. Most other fast-growing (dangerous) Lymphomas are curable. On the other hand, slow-growing Lymphomas are incurable but not dangerous. Unfortunately, MCL generally is both incurable and dangerous. However, hope may be on the horizon for patients that are suffering from MCL.

Chris Kavadas has experienced two types of MCL treatment, standard chemotherapy + Stem Cell (bone marrow) transplant and the potential new MCL treatment, oral “targeted therapy” tablets. The first signs of his MCL were discovered in 2012 when Chris was 47 years old.

Chris said he first noticed something was off when he was experiencing teary eyes constantly. As a tradesman, Chris initially brushed it off to his profession. Finally, after 8 months and no relief, Chris scheduled an appointment with an ophthalmologist who immediately noticed an irregularity on the inside of his eyelid. This led her to order a biopsy which revealed that Chris had MCL.

The same day Chris’s ophthalmologist booked him to see a haematologist. The realisation of a cancer diagnosis hit him all at once, ‘I was sort of unaware of what she was talking about, but basically life changed when she said I would have to do chemo sessions,’ recalls Chris.

Chris’s haematologist at the time decided to put him on the strongest dose of conventional chemotherapy available, Hyper-CVAD. Because MCL is an incurable and deadly blood cancer this option is considered the standard of care in patients who are deemed fit enough to withstand it.

Although Chris handled the initial chemotherapy well eventually it started to take a toll when it got to the second half of the treatment with the bone marrow stem cell transplant. ‘I was strong enough for the standard chemotherapy and I did take it, but when I had the stem cell transplant that was a little bit different. That changed things,’ said Chris.

After the first round of chemotherapy, Chris had to have his stem cells extracted through an apheresis machine. This process involves needle injections in the stomach to stimulate release of stem cells from the bone marrow, which are then collected by “washing” the blood through a machine.

The first half of chemo wore Chris’s body down and weakened his immune system, it left him to deal with pretty intense side effects after his stem cell transfusion. ‘For a few weeks I had nausea, high fevers and hallucinations. I also had a tingling in my legs and a little bit in my hands due to the chemo I was taking,’ said Chris.

The effects from the second round of chemo were stronger because Chris’s immune system had to be wiped out in order to put the new stem cells into his body. His immune system was so weak that he had to be isolated from other patients in the chemotherapy ward. ‘I was put into a special room where the doctors and my family was coming in with full hazmat suits with gloves and masks. That was probably the most difficult time for me.’

There was a certain point for Chris that rattled him more than any other time in the treatment process. ‘That second round at Peter Mac was very much different in that the strength of the chemo stripped the lining of my esophagus. At one point I went to drink a glass of water and I vomited blood.’

Although the Hyper-CVAD treatment was long and tough in the end it was success in sending Chris’s CML into remission.

Chris continued to stay in remission until 2015 when he started to notice his body to flare up again. This time there was an issue with his colon. He urged his doctor to organise a colonoscopy which showed that his Lymphoma had returned.

Since his body had already undergone the most intense chemotherapy regimen possible, his haematologist said there was nothing more that could be done. Coincidently, his doctor knew of a clinical trial that was available for patients that had a recurrence of their Mantle Cell Lymphoma.

It was then when Chris met Professor and Disease Group Lead at Peter Mac Constantine Tam and was put on the AIM study. The AIM study was designed and conducted by Prof Tam. Instead of intense chemotherapy, this study combined two highly effective oral targeted drugs called Ibrutinib and Venetoclax.

These drugs also led Chris to deal with some side effects. ‘I was fairly nauseous and had thin blood. Any sort of scratch would make me bleed easily.’

The side effects were a small price to pay for the result that Chris had with this new treatment. ‘I was absolutely blown away,’ said Chris. After two months of starting the drugs Chris went in for another Colonoscopy which showed no signs of Lymphoma. ‘I could not believe the effect those pills had on my tumors, it was unbelievable.’

Prof Tam said that after four months of the oral tablets Chris was in such a deep remission that their most sensitive test which is capable of finding one cancer cell in 100,000 normal cells even came back negative.

Chris’s cancer continued to stay in remission, and after a year and a half of taking the oral drugs he was able to stop oral treatment as Prof Tam and his team could not find any cancer cells in his body. More than 2.5 years after stopping all treatment, Chris remains free of cancer even on the most sensitive tests.

This sort of result helped to get the AIM study published in the New England Journal of Medicine in 2018. Additionally, Prof Tam’s team was able to discover a groundbreaking finding that got published in Nature Medicine. This finding revealed a new way in which cancer resists chemotherapy.

Prof Tam said through this they were able to discover how to overcome resistance in the few patients who didn’t respond to the study, which led to the Australian Government to fund the follow-up study, AIM2. At the moment is currently being designed by Prof Tam.

It is due to patients like Chris who are brave enough to enroll in clinical trials that doctors like Prof Tam are able to make advancements in medicine. ‘When I was taking Con’s drugs all I could think about was how these drugs are going to affect so many people,’ said Chris.

Chris suggests to others that clinical trials should definitely be considered for those who might be at the end of the road with other treatments. ‘My sincerest advice is to enroll in a clinical program such as Con’s,’ said Chris. ‘I would not be alive today if it wasn’t for Con and the clinical trial.’

16/07/2020
by Mackenzie Gignac

Receiving the news of a cancer diagnosis can be heavy news to bear. A common source of stress for patients are the worries about undergoing chemotherapy treatment. Although chemotherapy generally comes with side effects, these effects are manageable. Dr. Stephen Walker, Haematology Registrar at St Vincent’s Hospital Melbourne, explains more about chemotherapy’s common side effects and how they can be managed.

What are Common Side Effects I can expect with Chemotherapy?

The most common chemotherapy regimen that is used for blood cancers is R-CHOP, which is a combination of standard chemotherapy agents and an immunotherapy agent, Rituximab. With R-CHOP patients do sometimes experience immediate side effects that occur on the day of chemotherapy treatment. Because of the use of immunotherapy, patients potentially could experience reactions from the infusion such as fever, chills, rash, or shortness of breath. These are managed by slowing or temporarily interrupting the rituximab infusion by experienced nurses, who are constantly watching the patient for infusion reactions. Nausea (sickness) is another common concern of patients. The reality is that the drugs we use to prevent nausea these days are extremely effective, and therefore most patients experience no or little nausea during chemotherapy, provided they take their preventive medications as prescribed.

Other side effects might occur days to weeks following the chemotherapy treatment. Patients might find that they are more lethargic or tired than usual. Dr. Walker says that these symptoms might start to be noticed over time, ‘Lethargy and fatigue is often cumulative and can happen with later cycles of chemotherapy as well.’ Another potential toxicity to be aware of is risk of infection due to Neutropenia (low white cells, the cells that fight infection in the body). ‘The risk is typically highest day 8-14 following chemotherapy, but does depend on which chemotherapy the patient is receiving,’ advises Dr. Walker.

What are my Options to Help Me Manage These Effects?

‘Chemotherapy can be difficult, but it should never be intolerable or cause profound suffering,’ says Dr. Walker. Side effects are common with chemotherapy, but they are not something you should suffer in silence about. ‘If it’s reaching that point then we need to change or adjust something in your treatment.’

‘Although there are general things that can be done, there needs to be a dynamic approach to symptoms as they arise,’ says Dr. Walker. It is important for patients to have a discussion with their doctor about any side effects they notice through treatment so that their doctor can tailor an approach to help them mitigate the toxicities of treatment.

However, there are some broad approaches that can be taken to combat the side effects of nausea and fatigue. Nausea is often treated through the use of anti-nausea medication. Doctors tend to prescribe anti-nausea medication preventively to try and reduce the risk of this response. This can then be further tailored to the patient’s symptoms.

Dr. Walker encourages light physical activity to fight against lethargy and fatigue. ‘Gentle activities such as going for a regular walk or a short bike ride are shown to be beneficial to patient’s lethargy and fatigue, but more strenuous exercise can be counterproductive,’ says Dr. Walker.

Do Side Effects get Worse with Each Treatment Cycle?

Not all symptoms get worse with subsequent cycles. Some side effects can get worse as treatment continues, but this varies on a patient-by-patient basis. Some patients can experience nerve damage from ongoing treatments, leading to a feeling of numbness in the fingers and toes.

Again, it is important to have an open discussion with your doctor about the side effects you are experiencing, so they can take a personalised approach to manage any side effects. ‘We really do rely on patients telling us what their symptoms and experiences have been like so that we can tailor the treatment to them,’ says Dr. Walker.

Do the Side Effects Differ Depending on Type and Stage of Cancer?

The stage and type of blood cancer will have an influence on what chemotherapy drugs your haematologist will choose for your treatment. Different drug agents present different side effects, so, yes side effects can vary depending on the type of cancer.

For instance, more aggressive types of Lymphoma such as Diffuse Large B Cell will require multiple agents to be put together in a multi-drug regimen to treat the cancer. Lower-grade Lymphomas can be treated with one or two drugs. ‘It’s not as simple as saying more drugs are more toxic, but generally if there are more agents then there is more potential for toxicities,’ says Dr. Walker.

How Long After Chemotherapy Will it Take to Feel Better?

The period of recovery often depends on the intensity of the chemotherapy regimen. ‘The ability for the bone marrow and more rapidly regenerating tissue to recover can happen over a period of 2-4 weeks,’ says Dr. Walker. Additionally, a full recovery in terms of energy, fatigue and getting back to normal life can take longer. Even at around 3-6 months after recovery patients often feel tired in a way they may not have felt prior to their diagnosis.

However, patients that remain physically active tend to have a quicker recovery than patients who are less active. Doing some physical activity on a semi-active basis is shown to be helpful for chemotherapy recovery to help return to a normal life.

How Much Time Should I Take Off Work or School to Deal with Chemo?

Dr. Walker says that this is very treatment-specific and needs to be addressed on a case-by-case discussion with your doctor. R-CHOP chemotherapy takes 4.5 months to complete and another few months to recover. Typically for an aggressive Lymphoma 6 months is reasonable. For some other treatment options, patients continue to work, just taking days off when they need to be in the hospital to receive chemotherapy.

Can the doctors at the Melbourne Blood Specialists help those seeking treatment for blood cancers?

Yes, when you are referred to the Melbourne Blood Specialists our haematologists will do a comprehensive review and tailor a treatment plan that works best for you.

08/07/2020
by Mackenzie Gignac

A red blood cell transfusion may be required for some patients who suffer from anaemia. Anaemia is when your body doesn’t have enough red blood cells or haemoglobin to function properly. Anaemia can leave you feeling fatigued or tired and can sometimes impact your brain or heart function so having the proper red blood cell count is critical.

Additionally, if one has a low platelet count they would potentially need a blood transfusion as well. A low platelet count can increase the chance of severe bleeding, especially internal bleeding.

Why are red blood cells important?

The blood in our system consists of three main types of blood cells - red cells, white cells and platelets. Each type of blood cells serve a different function for the body.

Red blood cells contain haemoglobin which help to carry oxygen around the body. White blood cells are immune cells that defend the body against infections as well as cancers. Platelets help the body coagulation whenever we injure ourselves by coming together to stop bleeding or bruising.

What types of blood transfusions are there?

There are two main types of blood transfusions:

  1. Red blood cell transfusion → for low haemoglobin
  2. Platelet transfusion → when there is a low platelet count

When would I need a blood transfusion?

St Vincent’s Hospital Clinical and Laboratory Haematologist Dr. Matthew Ku says that when haematologists are considering a blood transfusion for their patients, they look at the haemoglobin count to determine whether it’s necessary. If the blood count gets down below a certain level, it is deemed necessary to transfuse. However, doctors take into account many different factors before referring a patient to a blood transfusion. These factors include patient age, fitness level, morbidity, the underlying medical condition causing the anaemia and if the patient has any risk factors for transfusion.

What is the blood transfusion process like?

If your doctor has deemed a transfusion is necessary the patient must go through the pretransfusion testing process. This process ensures that the right blood group is given back to the patient. The patient’s blood is drawn and tested to see if there are any antibodies that give a particular bond and cell types. Also, the blood is cross-matched to ensure that the donor’s blood is compatible with the blood of the patient.

Where is the blood transfusion administered?

Once the blood transfusion has been successfully cross-matched, the blood transfusion process will move forward and be administered in a medical facility. The red blood cell transfusion takes about 2-3 hours. Platelet infusions come in smaller bags and can be given in an hour.

Throughout the transfusion, a medical team will be monitoring the patient’s temperature, blood pressure, oxygen and heart rate for any negative reaction to the transfusion.

Once the transfusion is finished the patient will be sent home and will schedule a follow-up to make sure that their blood levels have improved to an appropriate level. Overnight hospitalisation is not necessary unless the patient becomes unwell during the period of observation after the blood transfusion.

Will a patient have to fast for a blood transfusion?

No, fasting is not required for a red blood cell transfusion.

What are the benefits of having a blood transfusion?

If a patient has systematic anaemia, a blood transfusion could improve their wellbeing, energy level and organ, cardiac and vascular functions. For someone with low platelets, a blood transfusion can make sure that they have enough haemoglobin availability to stop bleeding if they injure themself.

For someone who is really sick, the transfusion can make them feel better quickly after it is administered. For people that require multiple long-term transfusions, such as those with Leukemia or bone marrow problems, the efficacy of the transfusions might wear off with the frequency in which the transfusions are administered.

Are there any risks with having a blood transfusion?

Dr. Ku listed a couple of potential risk factors that come with having a blood transfusion such as fluid/ iron overload, allergic reactions, bacteria/ virus infections or incompatible blood.

The Australian blood supply is considered to be very safe and some of the best in the world, so Dr. Ku mentions that side effects are not very common. However, one of the side effects can be a fluid or iron overload. This occurs when a patient get too much fluid or iron in their system because of multiple infusions. Dr. Ku says it is important to be monitored for fluid balance especially for those that have a history of cardiac issues, heart failure, bone marrow failure or kidney impairment.

Bacteria and virus infections are another rare side effect that come with having a blood transfusion. Bacteria infections are slightly more common with platelet infusions because they are kept at room temperature. There is also a slight chance a patient could have an allergic or anaphylactic reaction to some of the proteins from the transfusion.

Lastly, in rare cases, incompatible blood grouping can occur which can lead to a reaction from the patient. Dr. Ku says this is rare as the Australian hospitals do have multiple checks and balances in place to make sure incompatible blood is not given.

How often would anaemic patients require a blood transfusion?

The frequency in which anaemic patients would need a blood transfusion is dependent on the underlying medical condition that they are being treated for. People with bone marrow dysfunction, Leukemia or Myelodysplasia might require multiple long-term treatments. For someone that has a severe haemorrhage or trauma they might just require a top-up blood transfusion.

Are there any alternatives to a blood transfusion?

Yes, there are alternatives that can be given for patients that have low blood count due to a nutritional deficiency, Myelodysplasia or chronic kidney disease. For nutritional deficiencies such as iron or B12 deficiency, supplements can be given as an alternative. People who suffer from chronic kidney disease quite often lack endogenous erythropoietin in their blood, which can be corrected with a drug to help with blood production. It is similar with Myelodysplasia as medication can be given to improve their blood count.

Can the doctors at the Melbourne Blood Specialists help those seeking treatment for blood disorders?

Yes, when you are referred to MBS for a blood transfusion, our haematologists will do a comprehensive review. Our specialists will assess and manage the cause of your blood count deficiency. If a blood transfusion is needed, our specialists will refer you to the appropriate facility for your blood transfusion.

30/06/2020
by Mackenzie Gignac

An iron infusion is an effective treatment for iron deficiency. Iron is needed to make red blood cells or haemoglobin which carries oxygen from the lungs to the muscles, tissues and organs. Low iron levels cause tiredness and affect your ability to function. As the iron stores become depleted, the haemoglobin level drops, and this is called iron deficiency anaemia.

An iron infusion is a method used to treat iron deficiency. The purpose of an iron infusion is to improve the iron deficit by directly replenishing the body’s iron stores.

St Vincent’s haematologist expert, Dr. ShuhYing Tan, helps us learn more about how iron infusions work and what can be expected from those receiving one.

How is iron deficiency treated?

There are several ways to replace and restore iron stores in the body:

  1. Oral iron in the form of tablets or liquid
  2. Intravenous (IV) infusion.
  3. Intramuscular iron (injection into the muscle). This is painful, causes skin staining, and should be avoided.

Dr. Tan says that the use of oral iron is the most common way of replacing iron and is often suitable and effective.

Oral iron is not a suitable option for everyone. The intravenous method can be considered in certain circumstances such as:

  • Difficulty taking oral iron due to side effects
  • Unable to absorb oral iron
  • Ongoing blood loss exceeding the ability to restore iron levels with oral iron
  • When there is a need to replace iron stores quickly, for example, late in pregnancy or before a major surgery to avoid a need for blood transfusions
  • Individuals with chronic kidney disease receiving EPO hormonal treatment

What is an iron infusion?

Iron infusion is a treatment where iron is given through a vein and directly enters the bloodstream. It is also called intravenous (IV) iron. A needle or cannula is placed in the arm or the back of the hand, which is then connected to a drip with iron mixed in with a saline solution.

There are different IV iron preparations available; the most commonly used these days is Ferric Carboxymaltose (Ferinject). This is the most recent addition of IV iron, and the main advantage is the significantly shorter duration of infusion of no more than 15 minutes. It is also associated with a lower risk of having an allergic reaction.

Where is an iron infusion administered?

An iron infusion is carried out in a medical facility where trained health professionals can effectively manage side effects if any were to occur during or after the infusion.

No overnight hospitalisation stay is necessary with iron infusions. ‘Patients are generally in the hospital for no more than a couple of hours,’ says Dr. Tan. The infusion itself takes around 15 minutes, and after the treatment, there is a period of observation before the patient is discharged.

If you need multiple treatments and there was no reaction during the first infusion, subsequent treatments may be able to be given at your home by a trained nurse, if this service is available.

How many iron infusions will it take to properly restore my iron levels?

Dr. Tan states that a single treatment is often sufficient to restore the iron levels. The treatment can be repeated if needed; how often the treatment is needed varies depending on the condition that is causing the iron deficiency, and whether it persists. ‘For example, if the cause of iron deficiency is diet-related (vegetarian or vegan), it is quite possible that the individual will become iron deficient again,’ says Dr. Tan. ‘However, if the iron deficiency was due to bleeding, the individual may not develop iron deficiency again if the bleeding has stopped.’

What are the side effects of iron infusions?

Iron infusion is generally given without any major issues. About one out of ten patients can experience ‘flu-like’ symptoms, such as muscle or joint ache, headache or mild fever. This usually occurs a couple of days after the infusion and settles with Panadol or Nurofen. Other common side effects include feeling sick or nausea, or a metallic taste, which should resolve after a few days.

An uncommon but *important* side effect to note is brown staining of the skin due to leakage of iron into tissues around the needle or drip site. The staining can be permanent. You should inform the doctor or nurse immediately if you experience any discomfort, burning, redness or swelling at the needle site.

A rare side effect is an allergic reaction or anaphylaxis to the iron infusion. This is the reason why the treatment is given at a medical facility with staff and resources available to manage this.

How would I prepare for an iron infusion? Do I need to fast?

Fasting is not required for the procedure, and you can take all of your regular medications for the day. Patients will be able to drive home and continue on with your normal activities after the infusion.

However, if you have an unexpected reaction, you will need to have someone else take you home. ‘You will be observed for longer in hospital and can only be discharged when you are medically stable,’ says Dr. Tan.

How long after my iron infusion will I start to feel better?

Your iron levels will be restored directly right after the infusion, however, it can take up to two weeks before you start to notice a difference and feel better.

What are the benefits & risks of an iron infusion?

An iron infusion is an effective and rapid way to replenish the body’s iron stores and the cost is covered by the pharmaceutical benefit scheme (PBS). The risks of an iron infusion are the side effects listed above.

Can the doctors at the Melbourne Blood Specialists help those seeking treatment for iron disorders?

Yes, when you are referred to MBS for an iron infusion, our haematologists will do a comprehensive review. Our specialists will assess and manage the cause of your iron deficiency. If an iron infusion is needed, our specialists will refer you to an appropriate facility.

Enrolling in a clinical trial can be an intimidating idea for some who are seeking treatment for their medical condition. However, there is actually a hidden benefit for those who feel courageous enough to enroll.

Clinical trials are run with the help of study coordinators. These coordinators are assigned to be the middleman between the patients, doctors, and the pharmaceutical company sponsoring the trial drug. Study coordinators help guide patients throughout the whole trial and guide them through all of their care, from the start of the trial to finish.

‘We monitor their progress closely, from the moment they get on the trial to the moment they come off,’ says Anupa Dey, who works in the clinical haematology unit as clinical trial coordinator at St. Vincent’s Hospital in Melbourne. ‘Other standard of care options don’t really have a coordinator touching base with them as frequently.’

Patients are seen much more frequently throughout a clinical trial than they would be on a standard care chemotherapy option. Because of this study coordinators are able to build a closer and more unique bond with their patients.

‘We see the patients once a week, so we can really focus on their concerns,’ says Dey. Study coordinators allow the patients to receive close to instant feedback about their worries. ‘If a patient brings up a side effect with me, I am able to get in contact with the doctor immediately instead of them having to wait a month.’

This kind of instant feedback can help to relieve anxiety and provide comfort for patients as they know they have an extra professional providing an additional layer of support. Often study coordinators provide direct lines of communication to their patients to allow their patients to come to them with any concerns, ‘they have our numbers and email addresses, so that way we can stay in close link with each other,’ says Dey. ‘We do build that bond with them, so they feel like they can trust us and tell us things.’

This kind of close connection with the patients is one of the reasons Dey says she enjoys her line of work. ‘I love working with the patients because you feel like you’re making a positive impact on somebody. You do see a lot of lives changing which is fantastic,’ she says.

Dey says another positive aspect is getting to work firsthand with new cutting edge drugs that will shape the future of care for patients. ‘Clinical trials have a massive impact on changing the treatment landscape of cancer in general. I love that aspect of it.’

Clinical trials that study coordinators work on help to improve the current treatment options for patients. In the trials that focus on cancer treatments, these trials study new targeted therapy options.

‘Normal chemotherapy doesn’t discriminate between normal and cancer-inducing cells,’ says Dey. Traditional chemotherapy often leaves patients dealing with a lot of side effects, but the treatments that are being studied now have reduced side effects by focusing on more targeted therapy. ‘Targeted treatment specifically targets the cancer-inducing cells which means less side effects such as nausea, hair loss, things like that,’ says Dey.

Additionally, these targeted therapies are being tested now so they can be listed on the pharmaceutical benefits scheme in the future. Currently, they are not widely available for medical use. However, this is one of the benefits of choosing to enroll in a clinical trial.

‘Being on a clinical trial gives you access to medications you wouldn’t otherwise have access to,’ says Dey. ‘That’s a win for the patient, because they are getting something with hopefully fewer side effects.’

Enrolling in a clinical trial is a good option for multiple reasons, ‘There are a lot of benefits to a clinical trial, it’s not just a novel drug, it’s also everything that comes with it, especially from a support perspective,’ says Dey.

Aside from monitoring and reporting their progress in the hospital, study coordinators also manage the care of their patients in other ways. ‘We do everything from arranging their taxis, to organising their accommodation, to their reimbursements for travel,’ says Dey.

Additionally, a lot of times patients are unaware that there are additional third-party support options for them. ‘It can be so daunting not having that support,’ says Dey. She says that organisations such as the Leukemia Foundation or the Red Cross offer support services for those in need.

Along with doctors, study coordinators take a patient-centered approach to their work. ‘As a coordinator, almost all the coordinators have a passion for clinical trials and really invest their time in helping the patient they have,’ says Dey.

‘I see my role as study coordinator as giving the patient access to something they otherwise wouldn’t have access to. It’s a privilege to work with the patients and to hear their stories.’

Multiple Myeloma (MM) is a blood disease that affects around 18,000-20,000 Australians each year. Initially, the diagnosis might be ill-received when patients hear that this disease is incurable. However, there has been a lot of advancements in treating this particular condition. New clinical trials that focus on treating MM have extended the life expectancy and quality in those diagnosed.

In November of 2018, Keith Halge received news that MM was found in his body, the same disease that affected his mother as well. Because of this, he had a decent amount of knowledge about the condition with one alarming aspect, ‘I knew it was not a cancer that would not go away,’ says Keith.

Keith’s mother was 75 years old when she received her diagnosis. He said from his perspective he saw some of the serious effects the condition had on her, so the news left him feeling devastated.

Luckily for Keith, Associate Professor Hang Quach and her team at St. Vincent’s were looking to bring a new treatment for MM to Australia. Currently, the combination of Bortezomib, Lenalidomide, and Dexamethasone are being used in the United States and Europe to treat people with Myeloma, but this combination has only received PBS reimbursement in Australia as of 1 June.

A powerful immune drug called Daratumumab is being added to this combination in credit to a clinical trial conducted by A/Prof Quach and her team at St. Vincent’s. This so-called ‘quadruplet’ combination is anticipated to be the way of the future because of its expectation to induce a deeper and more durable response than the current standard of care treatment.

‘I took the advice that this would be the best shot for me. There was obviously evidence in Europe that it had worked successively. ’ says Keith. He also says that A/Prof Quach’s knowledge, expertise and positivity gave him the confidence to give this treatment option a shot.

‘After speaking with Hang this wasn’t a ‘should I do this?’ it was a ‘yes, sign me up as quickly as you can.’’

Keith was the first person to undergo this clinical trial in Australia. His treatment included STEM cell transplant as well as Daratumumab Bortezomib and Lenalidomide.

Keith began his treatment of MM starting with a month of STEM cell transplant in February 2019. Now he receives maintenance treatment to keep cancer at bay and is taken through the use of daily oral drugs on top of a monthly intravenous injection that is administered at the hospital.

He credits the monthly hospital frequency as one of the sources of his courage to try the clinical trials. ‘It’s not like I’m waiting every one, two, or three years and hoping in the meantime everything is ok,’ says Keith. ‘They will know very quickly if there is a change to my condition and if they will need to change things.’

The drugs are working to battle the cancer but, unfortunately, this comes with additional physical impacts on the body. ‘My feet are somewhat numb and tingly all the time, so that’s uncomfortable,’ says Keith. Additionally, eating food might be a struggle at times dealing as the drugs affect food taste as well as the symptom of persistent nausea.

However, one of the most confronting symptoms Keith mentions is the hair loss due to the stem cell transplant. ‘Having to walk around in a beanie made me feel like more of a cancer patient,’ says Keith. ‘It creates the knowledge in your mind that you are a cancer patient.’

The good news is that after stem cell transplant, hair will start to return 6-12 months after the treatment ends. ‘My hair did come back after 6 months, and you know what I probably have a thicker head of hair now,’ says Keith.

However, there was more than just physical effects that Keith endured. ‘STEM cell transplant was one of the most difficult things I dealt with throughout the whole process,’ recalls Keith. The hospital isolation paired with nausea took a psychological toll on Keith. ‘It was tough, you need to tell yourself it’s only one month,’ says Keith.

Keith’s road to remission wasn’t achieved without complications. Before starting treatment, doctors found a myeloma tumour (plasmacytoma) in a sensitive area at the top of his spine. Keith had to undergo radiotherapy and surgery simultaneously.

Doctors went in for surgery to stabilise Keith’s neck with two rods and a titanium plate at the base of his scalp. These additions do not make life any easier for Keith. ‘It has severely restricted my level of movement in my neck to turn to either side,’ says Keith. ‘If I’m not feeling nauseous from medication then my neck is extremely stiff.’

However, Keith comments that although there are side effects they are manageable. ‘With this disease, there are incredible advancements and even with rods in my neck and medication, I am back at work,’ says Keith.

For any future MM patients, Keith offers a couple of words of advice to avoid Google. ‘You get on Google and it takes you to a fairly dark place,’ says Keith. ‘This will not be a disease that kills you in 3-5 years; it’s something that can be managed.’

Additionally, Keith encourages MM patients to wait and see what your medical professional has to say. ‘Trust your doctors, they are the experts and are trying to help you in any way they can,’ says Keith.

A/Prof Hang was one of the greatest comforts Keith had throughout his treatment process. ‘I know that getting ahold of a specialist is difficult to do, but I know that if I send her a message today in half an hour or an hour I would get a response from her,’ says Keith. ‘That is very comforting because you know that you’re not being abandoned, you’re not just a number.’

‘She actually goes above and beyond to make her patients feel comfortable and supported. There’s not a lot of specialists who do that, so I am lucky to have her on my team.’

Lastly, Keith also mentions that it is important that MM patients stay positive, ‘if you constantly think about your morbidity it becomes a bit of a cycle.’ He suggests trying to live as normal of a life as possible. ‘For me, it has been helpful in going back to work. The whole point of it [the treatment] is to live your life as normal as you can. So, you might as well do it,’ he says.

Normal life for Keith even includes doing some world travel. Keith had a trip to visit Europe for a month, which ultimately had to be canceled due to COVID-19. ‘The doctor had no problem with me going and enjoying that part of my life,’ says Keith.

‘They want you to live your life and be happy. They are doing a lot of the work to allow you to continue to be happy.’

There is hope for people who have been diagnosed with MM. While it is technically not a blood disease that can be cured new therapy options are able to help manage it, allowing patients to live a longer and healthier life than before.

For anyone looking to treat their MM diagnosis, our team of doctors at Melbourne Blood Specialists can access you for your specialised appropriate treatment plan.

Five years ago Peter Younis became the eighth human patient in the world to receive the experimental drug BGB-3111. Peter was first diagnosed with Waldenstroms Macroglobulinemia in 2004, however, he was able to get by on his condition until 2007 when his paraprotein levels began to rapidly increase.

Listening to his doctor’s advice Peter underwent four cycles of intensive chemotherapy. Following chemotherapy Peter’s bone marrow biopsy suggested there were very few malignant cells left in his bone marrow, and he was able to go back to living a normal life with no treatment.

Seven years later in 2014, Peter’s paraprotein levels began to rise again. At that time, Haematologist and disease group lead at Peter Mac Constantine Tam offered Peter the chance to enroll in a phase I clinical trial for BGB-3111. The drug was so new that when Peter was approached by Professor Tam about enrolling in the trial, the right dosage amount was still being tested.

Prof Tam says that for his trial Zanubrutinib (BGB-3111) dose started as 40mg daily and then went up to 80mg, which is what Peter started with. Thanks to the study Peter participated in, we now know that the drug is most effective at a dose of 160mg twice daily.

Peter said that the decision to try BGB-3111 to treat his condition was more of a rational decision for him than one out of courage. ‘I wasn’t going to die next week. I figured I had some time,’ recalls Peter.

Another factor that Peter took into account was the similarity of Ibrutinib, the current drug used to treat Waldenstroms, and the new drug he was going to be using. ‘The new drug I was given was a new molecule of a BTK inhibitor, so it was likely going to have some effect,’ says Peter.

Additionally, Peter says that he was interested in the trial as a way to help those in the scientific community. ‘That probably made me choose this decision,’ recalls Peter. ‘I was contributing to the greater scientific good.’

Prof Tam says that the staging of clinical trials usually follows a similar format. ‘Phase I is about determining the right dose and side effect profile of the drug,’ says Tam.

After the correct dose is determined, phase II focuses on getting more experience with the drug. If there is enough evidence to progress then it goes to phase III.

This phase is focused on licensing the drug by going head-to-head with the world’s best-determined treatment option for the medical condition in focus. Prof Tam says by this point, ‘we know the drug, we know the dose, but how does it compare with the best of the best?’

Phase III involves an international randomised study where patients are randomly assigned the new drug or the previous best standard of care to see in a direct comparison which one is better. ‘It makes it a fair comparison because there is no bias,’ says Prof Tam.

Thanks to Peter’s courage to partake in the clinical trial, Zanubrutinib has made its way through phase III and is on its way to seek approval from the FDA to treat the blood disease Waldenstroms Macroglobulinemia.

Phase III of the Zanubrutinib study is called ASPEN and compares this drug to the current standard drug treatment, Ibrutinib. Prof Tam recently revealed his ASPEN findings at the American Society of Clinical Oncology Conference.

ASPEN compares the two drugs head-to-head. Zanubrutinib and Ibrutinib are similar. They come from the same class of drugs and hit the same target, the BTK inhibitor.

Another similarity is their side effect profile which includes high blood pressure, bleeding and heart arrhythmia. Although both these drugs are very similar Prof Tam suggests that Zanubrutinib is like a cleaner version of Ibrutinib, meaning it has the potential for less side-effects.

They are both similar in terms of effectiveness, however, the side effects that patients faced when on Zanubrutinib are much less significant. ‘The most prominent side effect was the heart going out of rhythm which 18% with Ibrutinib and only 3% with Zanubrutinib, so a six-fold difference in the rate of the heart going out of rhythm,’ says Prof Tam.

Prof Tam says that his key finding throughout the ASPEN study was the difference in side effect rate in favor of Zanubrutinib. ‘Because of fewer side effects, patients were able to take the drug for longer and therefore had a better quality of life,’ says Prof Tam.

The world’s first 25 patients were treated with this drug received the treatment in Melbourne under the supervision of Prof Tam and his colleagues. Prof Tam expresses great personal satisfaction in seeing Zanubrutinib progress throughout its whole life cycle. ‘We took it from a chemical, designed the first study, gave it to the first humans, and now see the drug successfully complete phase III testing. The type of success is every cancer researcher’s dream.’

Prof Tam says he credits this breakthrough to those like Peter who take a leap of faith to enroll in these clinical studies. ‘It’s because of patients like Peter who put their lives and bodies on the line that we can get to where we are today.’

Currently, Peter is still taking an oral dose of Zanubrutinib every day and has seen virtually no side effects. His cancer continues to remain in remission.

02/06/2020
by Mackenzie Gignac

COVID-19 Update: June 2020

We are cautiously getting back towards normality as the rest of the world struggles to deal with the challenges of COVID-19 infection. Australia is in the enviable position of having very low infection rates, allowing cautious relaxation of restrictions and a slow return towards normal life. Since the onset of the outbreak, Victoria has conducted over 500,000 COVID-19 tests, 0.3% of which returned positive. With the notable exception of isolated “clusters” of infections (such as the one at the Cedar Meats factory), community transmission (meaning we don’t know how a person caught the virus) is very uncommon in Victoria at the moment, with less than 10 new cases per day.

What does this mean for our patients?

  • As the restrictions are relaxed and people gather in larger crowds, community transmissions are bound to rise. Hopefully these new clusters can be identified and contained quickly by public health officials. However, if we get a substantial number of new cases (say more than 100 per day), then it is an indication that the virus is more widespread than we think, and for patients at particular risk (eg over 70 years old, or have a blood cancer) to take stringent precautions again.
  • In the meantime, one has to get on with life. So, keep on social distancing, avoid large crowds, clean your hands often, and if you are at particular risk (eg over 70 years old, or have a blood cancer) consider wearing a mask in crowded indoor areas.
  • What about kids and grandkids? Once again, one has to get on with life accepting cautious risks. For reasons that are unclear, COVID-19 is relatively uncommon in children. In Victoria, only 58 cases have been recorded in children 0 to 14 years old. This is only 3.5% of the total confirmed cases in Victoria. So, contact with kids is likely ok. However, if the case numbers start to climb after school returns, we may need to take stringent precautions again.

    An update on COVID treatments:

    A large study comparing Remdesivir to placebo (the ACTT Study) was discussed at our last COVID-19 update, and this study is now published in New England Journal of Medicine. The conclusions remain the same – recovery time is faster in patients treated with Remdesivir (11 days, compared with 15 days for placebo), but the chances of surviving the infection have not been proven to be better to date.

  • Not such good news for Hydroxychloroquine. A large study published in Lancet showed that patients receiving Hydroxychloroquine had higher chances of dying, due to heart problems which are known side-effects of the drug.

So as before, prevention is the key. Stay safe, and we hope you (cautiously) enjoy your new freedoms.

Immunotherapy has revolutionised the way haematological cancers are treated. Immunotherapy works by using the patient’s own immune system to fight against cancer cells. St. Vincent’s Hospital Clinical and Laboratory Haematologist Dr. Matthew Ku says that within our blood there are a variety of cells that help defend us against infections and cancers, such as T Cells and Natural Killer (NK) Cells. These cells act as “policemen” to detect and eliminate cancer cells before they can take hold in our body.

In cases where cancer occurs, the cancer is able to hide from these “policemen” T and NK Cells, or resist their attack. Immunotherapy refers to a group of treatments that work by helping these policemen cells by making them stronger, helping them “see” the cancer better, or by genetically modifying them into an “super-policemen” army capable of destroying cancer even if the cancer tries to resist and fight back.

Dr. Ku says that the idea of immunotherapy is to work towards making the immune system stronger while weakening the tumour cells. Furthermore, ‘immunotherapy is not just about immune and tumour cells; it’s about the tumour microenvironment as well.’

Dr. Ku says that immunotherapy treatments are not limited to just blood cancers. ‘Within Australia, immunotherapy is used prominently in treating other cancers such as melanomas.’

What types of immunotherapy treatments are available?

There are four main immunotherapy strategies currently available according to Dr. Ku.

1. Drugs that generally strengthen the immune system

Immunomodulatory drugs and CelMODS are examples of drugs that generally strengthen the immune system. These drugs stimulate a group of immune cells in the body called T cells and Natural killer cells, independent of their other activities against cancers. The generalised increase in immune functions means that there is better immune surveillance against cancers, and that there is a less likely chance that cancers can escape detection and destruction by the immune system. Dr Ku says that lenalidomide and pomalidomide are immunomodulatory drugs that are commonly used for multiple myeloma, a blood cancer that has seen many fantastic new therapies coming through.

Another class of drugs is called monoclonal antibodies, and they act by targeting the cancer cell surface structure. An example of this would be rituximab, which attacks the CD20 molecule on B cell lymphoma, and destroys the lymphoma cells via different immune mediated pathways.

2. Checkpoint Inhibition

Another immunotherapy strategy Dr. Ku mentioned is checkpoint inhibition. Immune checkpoints are a healthy part of the immune system. They work to regulate the body’s immune response so that it is not overactive unnecessarily, thus damaging healthy cells in the body.

Many cancers hijack this normal immune signal to hide themselves from the immune system. When checkpoint and partner protein on the cancer cell come together, they send an ‘off’ signal to T (policemen) Cells which can prevent one’s immune system from destroying the cancer cell. Checkpoint inhibitors work by stopping the checkpoint partner proteins on cancer cells from bonding with the checkpoint proteins on T Cells. These drugs prevent the ‘off’ signal from being sent which allows T Cells to kill off the cancer cells that appear in one’s immune system.

Dr. Ku says that checkpoint inhibitor immunotherapy is used to treat lymphomas, melanomas and lung cancers. Checkpoint inhibitors have shown to be effective against classical Hodgkin lymphomas. In effect, they yank away the “cloak of invisibility” that the cancer uses to hide itself, and allows the healthy immune cells to see and destroy the cancer.

3. T Cell Engagers

The third strategy Dr. Ku mentions isT Cell Engagers. These drugs are like guided missiles that directly bring the host’s immune cells next to the cancer cells. Dr. Ku describes the process, ‘T Cell Engagers are modules that hold onto T Cells with one arm and onto cancer cells with the other arm. This brings them together, creating T Cell immunity against the cancer cells.’

Dr. Ku has directly seen the positive results that have come from T Cell Engager immunotherapy clinical studies. ‘We at St. Vincent’s have a couple of studies using the T Cell engagers which have shown to be very effective. The results were even presented at one of the international lymphoma conferences last year,’ says Dr. Ku.

4. CAR T Cell Therapy

The fourth strategy that is at the forefront of immunotherapy is CAR T Cell therapy. Dr. Ku explains that CAR T Cell therapy works by collecting the patient’s own T Cells through an apheresis machine. Then the T Cells are genetically engineered to be super-strong, single-minded “super-policemen” that target cancer cells. An army of these cells are formed by growing them in the laboratory, and they are then reinfused back into the patient. However, ‘CAR T Cells are not widely available at the moment,’ urges Dr. Ku.

Amongst all these therapeutic options the CAR T and T Cell Engagers are some of the most effective treatment options available now, especially for diffuse large B cell lymphoma and follicular lymphoma. ‘T Cell Engagers and CAR T are cutting edge therapies for lymphomas and myeloma at the moment,’ says Dr. Ku. The number of clinical trials that focus on these two groups of agents will continue to grow exponentially. ‘We are at the start of the golden era in immunotherapies,’ says Dr Ku. ‘T Cell Engagers and CAR T are the new kids on the block, but they are also the ones that are attracting the most amount of interest because they appear to be the most effective.’

Dr. Ku says both CAR T and T Cell Engagers have their pros and cons. ‘CAR T works well, but has a higher risk of toxicity and side effects,’ says Dr. Ku. Harvesting the T Cells also requires more effort and can be more expensive. In comparison, T Cell Engagers might not be proven to be as effective yet, but they appear to be better tolerated, easier to administer and require less waiting time says Dr. Ku.

Are there any side effects?

Dr. Ku warns that there are unique side effects that might potentially come with CAR T and T Cell Engagers. Dr. Ku says that in his opinion, ‘standard chemotherapy treatments have more side effects’ than immunotherapy options. Dr. Ku says that patients may need to stay in the hospital for longer than chemotherapy because of the potential side effects.

1. Cytokine Release Syndrome - CRS

CRS is when the patient’s immune system is kicked into overdrive and starts to affect the other parts of the body, aside from the targeted lymphoma and leukemia cells. Dr. Ku says common CRS features include fevers, low blood pressure and low oxygen levels in the blood. As result, some patients might require intensive care support to manage a potential CRS symptom episode. However, Dr. Ku encourages that, ‘there are effective medications we can give to patients to control CRS.’

2. Neurotoxicity

Another main side effect that a patient might have to endure is neurotoxicity, which could affect higher centres within the brain thus hindering a patient’s speech or ability to write. ‘Some people will need neurological support or management from the neurologist because of neurotoxicity.’ Again, Dr. Ku advises that doctors do have the resources to help manage this side effect. Additionally, in terms of brain function CAR T and T Cell Engagers are not known to have any long-term, permanent adverse effects.

Which Immunotherapy treatments have been approved on the Pharmaceutical Benefit Scheme (PBS) in Australia?

In Australia, PeterMac is the only hospital that is conducting publicly funded CAR T therapies. Otherwise, all other CAR T therapies are being done as clinical trials at select institutions.

Dr. Ku advises that there are no publicly funded T Cell Engager treatments.

‘Lenalidomide and Pomalidomideare funded by PBS for myeloma,’ says Dr. Ku.

In regards to checkpoint inhibitors they are currently funded for Hodgkin lymphoma says Dr. Ku.

Where can I go if I have lymphoma and I am interested in considering new immunotherapies?

Dr. Ku says there is good news for cancer patients here in Australia. ‘This is the new era of cancer therapy. In Victoria in particular there are many big centres conducting immunotherapy trials,’ encourages Dr. Ku.

If you are a patient who is looking for novel treatment options, Dr. Ku advises you to contact your specialist about the trial options available. At Melbourne Blood Specialists our doctors can link you up to the appropriate health centre for blood cancer treatment. If you are interested in exploring the option of immunotherapy please contact us at Melbourne Blood Specialists today.

In medicine, new treatment options are constantly being developed to achieve a better life for patients.

One new therapy that has received traction in recent years is Chimeric Antigen Receptor (CAR) T-Cell therapy. CAR T-Cell therapy is a form of immunotherapy, where your body uses its own immune system to directly target cancer cells.

As it stands this new form of treatment is very new in Australia and is only available as a treatment option for certain types of Lymphomas and Leukemias. However, some doctors see CAR T-Cell as the way of the future for a broad variety of blood cancer treatments.

Professor and clinical lead for Low-Grade Lymphomas at Peter MacCallum Cancer Centre Constantine (Con) Tam was able to secure a clinical trial for this cutting edge treatment option for one of his Lymphoma patients, Christine Freestone.

Christine was first diagnosed with stage III non-Hodgkin Lymphoma in 2016. Prof Tam led the medical team that treated Christine for her Lymphoma. Tam said given her age at the time of diagnosis the first treatment attempt was to use full-body radiation.

There were many negative effects that Christine suffered throughout her treatment, one of these being the burning pain in her throat. ‘You can’t physically eat, it was just too painful,’ she said. ‘I lived on jelly and drinks. You couldn’t eat. You couldn’t swallow.’

Christine also noted that radiation caused her skin to peel, which is something people tend to overlook when it comes to radiation treatment. ‘Some things which people don’t think about, is it’s like having a terrible sunburn,’ she said. ‘My arms, my back, they all were peeling.’

The radiation treatment option was meant to kill off the cancer for good. So when Christine’s non-Hodgkin Lymphoma came back this time in stage IV, it came as a shock to her and her family.

‘You think you got through it alright the first time. You’re hoping you don’t have to do it again,’ she said.

This time Christine underwent six intensive cycles of chemotherapy. The treatment was so hard on her body that it made her physically ill.

Christine battled health complications as the rounds of chemotherapy treatment continued. In the last two rounds of treatment, she had to be admitted to the hospital on both occasions due to infections from the RCHOP chemotherapy drugs.

‘It’s just so hard on your body,’ Christine said. ‘I don’t think people understand it unless they’ve been through it.’

During this time the effects of cancer treatment not only had physical effects but strenuous psychological effects as well.

‘You feel sort of isolated, especially when you are at the hospital and there is no one around,’ she said. ‘That’s the hardest part. You could be feeling the worse that you could possibly be, and then you start to have breakdowns.’

On top of the isolation, the treatment took her away from her children. Christine lives in rural Victoria and had all her treatment in Melbourne. ‘Leaving my kids at home and not being around them… that was hard,’ Christine said.

After her six cycles of chemotherapy, Christine relapsed a third time. ‘I still didn’t feel 100 percent, but I just put it down to the chemotherapy treatment,’ Christine said.

This time Prof Tam recommended an anticancer treatment still new to Australia, CAR T-Cell therapy treatment.

The CAR T-Cell treatment process is a minor medical miracle. First, the patient’s own T cells are collected from the patient via an apheresis blood draw. Then, the cells are sent to a medical lab that has the capability to reengineer DNA and insert chimeric antigen receptors (CARs) into the T cells, turning them into “robotic soldiers” dedicated to attacking lymphoma. Once these cells are made, they are sent back over to be infused into the patient. This is done in a one-off injection dose.

Prof Tam was the Australian lead for the international team that developed CAR T-cell treatment for diffuse large cell lymphoma. However, for Christine’s type of lymphoma, the only way to access CAR T-cells was to join a clinical trial under Prof Tam’s supervision.

Christine explains her experience during the CAR T-Cell clinical trial, ‘CAR T-Cell was a once-off treatment. It’s not like you’re going in every three weeks like chemo,’ she said. Christine said with the constant rounds of chemotherapy, she really started to dread each chemo cycle. ‘Chemo makes you feel sick from the minute it hits your blood,’ she said.

The difference between Christine’s chemotherapy versus her CAR T-Cell treatment was like night and day. ‘With chemotherapy you’re nauseous all the time, always feeling sick and tired. With CAR T it’s so much easier. I felt good all of the sudden,’ she said.

Christine underwent CAR T-Cell therapy in May 2019 and achieved complete remission of her stage IV non-Hodgkin Lymphoma.

Since this treatment started, Christine has had minimal side effects and is doing the best she’s ever been since first being diagnosed with cancer in 2016. ‘My cancer is gone,’ she said. ‘If you can get into the trials then do it. It has taken my cancer away.’

Christine said her willingness to pursue the CAR T-Cell treatment stems from a selfless desire to help others as well. ‘It might take a few of us to do the trials, but it will make it easier for others in the future,’ she said. ‘For others to get access to these treatments, it’s worth it.’

CAR T-Cell therapy is still very, very new in the medical world. However, this line of treatment is set to be at the forefront of treatment for blood cancers, and this highly specialised option has the potential to offer future cancer patients a brighter and easier outcome by harnessing the power of their own immune systems.

Myelodysplastic syndrome (MDS) can be a tricky blood disease to explain. Dr. Shuh Tan, haematologist at St. Vincent’s hospital, is an expert in her field and specialises in treating MDS.

Dr. Tan helped guide us through the basics of understanding the diagnosis, what can be expected with treatment, and what research is currently being done on MDS to further our understanding and treatment options.

What is MDS?

MDS is a condition where the bone marrow does not produce enough healthy blood cells. It is a form of blood cancer caused by genetic damage in the primitive cells (stem cells) in the bone marrow.

Dr. Tan says that people with MDS have an active bone marrow. However, the blood cells that are made are defective and do not survive for very long, resulting in low blood counts in the circulation.

Patients with MDS often have anaemia (low red blood cells). Additionally, they can also have neutropenia (low white blood cells) and/or thrombocytopenia (low platelets).

In those with advanced MDS, the blood cells also do not fully mature. The bone marrow accumulates immature blood cells called blasts, and when this exceeds 20 percent, it is called acute leukaemia (AML). Overall, approximately 1-out-of-3 people with MDS will progress to AML.

There are many subtypes of MDS and can broadly be divided into two groups:

1. Low risk/ Early MDS
2. High risk/ Advanced MDS

What is the bone marrow?

Dr. Tan gives us some explanation about the function of the bone marrow. ‘The bone marrow is the ‘factory’ of blood cells, producing around 7 billion blood cells per hour,’ says Dr. Tan.

She says that the bone marrow contains stem cells that can be mature into any type of blood cells. Each blood cell lives for a certain amount of time, and is removed by the body as it gets old and damaged. The bone marrow in turn replenishes and releases fresh blood cells into the circulation.

There are three main types of blood cells:

  1. Red blood cells that carry oxygen to muscles and tissues
  2. White blood cells that help fight against infection
  3. Platelets that help stops bleeding

What causes MDS?

MDS is invariably caused by genetic damage to the stem cells in the bone marrow, called somatic mutations. Dr. Tan describes this as a change in the ‘programming of the factory.’

She says that the exact cause of this is not entirely clear. However, in recent years, advances in research have shown that aging plays a role in the genetic changes and development of this condition.

This might explain why MDS is more common in older people, mostly affecting those over 60 years old.

The other risk factors for developing MDS include:

  • Prior chemotherapy or radiotherapy treatment
  • Chronic exposure to petrochemicals
  • Some rare congenital conditions

Is MDS curable?

Dr. Tan says that stem cells or bone marrow transplant using donor cells is the only potential for cure. However, this is a high-risk treatment that is only suitable to younger patients.

As most people with MDS are older, there is currently no known cure for the vast majority.

How will MDS affect my life?

The symptoms of MDS vary depending on which bloodlines are affected and the severity of the MDS.

Tiredness or fatigue is the most common symptom, especially in those with anaemia. Anaemia can also cause shortness of breath, dizziness, and reduced exercise capacity. Additionally, patients with low white blood cell counts are more vulnerable to infections. In those with low platelets, they may experience easy bruising and bleeding problems.

Some patients will also require regular hospital admissions for transfusions, or may be hospitalised due to severe infection.

Will my MDS require chemotherapy treatment?

Patients with early MDS may not require any treatment, and can be closely monitored.

In patients with significantly low blood counts, supportive care is one of the key focus in the management of this condition. This is aimed at improving symptoms through:

  • Blood transfusions
  • Platelet transfusions
  • Growth factor injections

Chemotherapy or disease modifying therapy options may be available for patients with advanced MDS. Some of these options include:

  1. Azacitdine or Vidaza is given as an injection under the skin for seven days every month.

  2. Dr. Tan says that this drug can slow down or stop the condition from getting worse. In some cases, it may also improve blood counts and reduce the need for transfusions. The treatment is effective in about 40-to-50 percent of patients and can be continued for as long as it is working.

  3. Lenalidomide or Revlimid is a tablet treatment used specifically for patients with 5q-syndrome subtype of MDS.

  4. Traditional chemotherapy is not often used since Azacitidine has become available. It is generally reserved for patients with very advanced MDS (MDS with excess blasts-2) or where MDS has transformed to AML.

Are there any other treatment options besides chemotherapy?

Dr. Tan advises that there are no other treatments available through the pharmaceutical benefit scheme (PBS) in Australia. Several new treatments are being developed for MDS, and these may be available through clinical trials. Some of these include:

  • Targeted therapy - in patients with specific genetic changes
  • Immunotherapy - that harnesses patients’ immune system to tackle the MDS cells
  • Small molecule inhibitors - that can direct the killing of MDS cells

These new approaches are smarter ways to treat the disease. ‘They tackle the genetic changes that drive the disease, and disarm the machinery that help MDS cells survive,’ says Dr. Tan.

Through many years of research, there have been significant advances in understanding of MDS, notably the unravelling of the genetic complexity of this condition. ‘The complexity of MDS is why traditional chemotherapy has not been as effective,’ says Dr. Tan.

As the MDS & AML lead at St. Vincent’s Hospital,, what have been some of your key findings or major breakthroughs as an academic researcher?

Dr. Tan has a keen interest in MDS and AML. ‘I am drawn to the genetic changes that underpin these conditions. They are similar, but MDS is far more complex,’ says Dr. Tan.

Dr. Tan says she focused on MDS for her PhD research. She delved into how genetic mutation changes composition of stem cells in the bone marrow to result in MDS. Using this knowledge, she was able to curate models of MDS.

‘I generated lab models of MDS and used these to screen tens of thousands of drug compounds to discover potential new drugs to treat MDS.’ She hopes that this will eventually be of benefit, although it will take many more years before any of the newly discovered drugs can be tested on patients.

She also leads MDS and AML clinical trials at St. Vincent’s Hospital in Melbourne. ‘We have clinical trials which allow patients earlier access to some of the new treatments available,’ says Dr. Tan. She is passionate about expanding clinical trials options for all patients, including making these treatment options more accessible for patients in rural areas. ‘I am inspired to improve treatment options and the outcome of patients living with MDS & AML.’

Remdesivir Receives United States Food and Drug Administration (FDA) Authorization to Treat COVID-19

We wrote about Remdesivir three weeks ago. This is an experimental anti-viral drug developed by Gilead Sciences, that was previously tried against Ebola and hepatitis without success. This drug works by blocking a class of enzymes (called RNA polymerases) across a broad range of viruses including COVID-19. At that time, the drug was only reported in a small number of patients who received the drug on compassionate access. Among these patients, the rate of death was at the lower end of what would be expected for patients with severe COVID-19 disease treated in a conventional manner (ie without antiviral drugs). So, there was a subtle signal that the drug may be useful, but it was not a game-changer.

The FDA has now given emergency use authorization for Remdesivir in the United States. Note that this is NOT the same as full approval of the drug. Full approval means the drug has been fully evaluated and shown to be safe and effective.

The current decision to allow emergency use is driven by the early results of a new study, where patients are randomly assigned to treatment with Remdesivir, or placebo. This kind of experiment is the only objective way to tell if the drug truly works or not.

So, what do we know about the results of this study?

  • Firstly, very little details are available about this study, as the study is not published in any medical journal as of today. This means that independent experts are currently reading the study report and making sure that the conclusions are correct.
  • We do know the study was coordinated by the National Institute of Health in the US, and that it started on February 21st, enrolling 1063 patients.
  • Patients who received Remdesivir recovered faster than those who received placebo – 11 days for Remdesivir, compared with 15 days for placebo. This difference is statistically proven to be real and not due to chance.
  • The rates of death appear to be lower in patients receiving Remdesivir (8.0% died) when compared with placebo (11.6% died). However, this difference is not statistically proven to be real, and could have happened by chance.

Under the current FDA authorisation, this drug cannot be taken to prevent COVID-19, but rather, can be only use din patients who are hospitalized with severe COVID-19 requiring oxygen or ventilation support, in the hope of a faster recovery.

The take home message is that the drug has some activity against COVID-19 but is not the same as antibiotics for normal infections, where if one receives antibiotics on time, we can normally expect a full recovery. The drug is a useful addition to normal care but is not a “magic bullet” against COVID-19. Even if we accept the death rates at face value, the most Remdesivir did was in reducing the chance of dying from COVID-19 from 1-in-9, to 1-in-12. It is not another penicillin.

The best thing to do is not to catch COVID-19 in the first place, so keep up the precautions as we relax social isolation across Australia.

Stay safe everybody

Professor Con Tam, Associate Professor Ali Bazargan, Associate Professor Hang Quach, Dr ShuhYing Tan, Dr Matthew Ku and all the staff from Melbourne Blood Specialists.

01/05/2020
by Mackenzie Gignac

COVID-19 remains to be a concern for everyone, especially those diagnosed with blood cancers. We spoke with Associate Professor Hang Quach who is a specialist in treating Multiple Myeloma to gain a greater understanding of the COVID-19 risks and measures that should be taken into account for anyone diagnosed with Myeloma.

How does COVID-19 affect people with blood cancers including multiple myeloma?

Having a blood cancer including myeloma does not necessarily change the risk or way in which a person catches COVID-19. However, having blood cancer does affect one’s immune system. Due to a weaker immune system, a person with blood cancer might have more severe symptoms and may be at a higher risk of ending up in intensive care if they catch COVID-19.

A/Prof Quach says that the best way to minimise the risk of COVID-19 for patients with multiple myeloma is through preventative measures and optimising general health and immune status through effective control of myeloma itself. This include:

  • Following social distancing guidelines
  • Proper cough & sneezing etiquette
  • Frequently washing your hands and avoid touching your face
  • Regular exercise and eating healthy
  • Some people with myeloma have low antibody levels and if this results in recurrent infection, infusions of antibodies harvested from blood donors (called immunoglobulins) are sometimes given every month to boost the immunity in general. We do not know whether or not this will specifically reduce the risk associated with COVID-19. People who are already receiving immunoglobulin by venous injections in the hospital can ask their haematologist if they can have it continued at home as an injection through the skin.
  • In people with myeloma that is progressing, one of the best ways to optimise the immune system is effective control of myeloma.

Will myeloma treatment increase the risk of contracting COVID-19?

‘In patients with active myeloma, the best defence against any infection, including COVID-19, is to effectively treat the myeloma itself,' says A/Prof Quach.

‘For patients with active myeloma, we need to offer the best treatment possible,' says A/Prof Quach. ‘However, how this is done will depend on the stage of the pandemic we are in and if there are sufficient hospital resources to deliver the type of treatment we need.’

I am due for Autologous Stem Cell Transplant (ASCT) should I proceed?

Autologous stem cell transplant (ASCT) remains an important part of initial treatment for fit patients who are diagnosed with myeloma. ‘It improves progression-free survival compared to a non-ASCT approach,’ says A/Prof Quach.

The decision to proceed or delay ASCT during the COVID-19 pandemic varies between different hospitals and is usually determined on a case-by-case basis. ‘It depends on the inpatient capacity of that hospital at the time of the pandemic. We don’t want to put a patient through a stem cell transplant when intensive care beds cannot be accessed if it is needed during the peak of the pandemic,’ says A/Prof Quach.

A/Prof Quach mentions that patients can remain on Bortezomib based therapy while awaiting for autologous stem cell transplant if this has to be delayed.

With Australia’s preliminary success in reducing the number of new COVID-19 cases, the expected peak of the pandemic is pushed out for some months. Some hospitals have therefore chosen to continue autologous cell transplants. ‘At St. Vincent's Hospital in Melbourne, we feel that there is a window, at this point, to offer autologous stem cell transplants to patients who are at higher risk before the peak of the pandemic occurs,’ says A/Prof Quach.

Can maintenance therapy continue after autologous stem cell transplant during the COVID-19 pandemic?

Maintenance therapy after stem cell transplant remains important because it has been shown to improve progression-free survival and overall survival compared to no maintenance, for people with myeloma. The usual maintenance therapy is with a drug called Revlimid (also known as lenalidomide)

‘Revlimid is not considered to be an immune suppressive drug. Given the fact it can be taken as a capsule by mouth at home, most haematologist will elect to continue maintenance therapy,’ mentions A/Prof Quach.

What about bone-strengthening treatment with Zometa or Pamidronate?

Bisphosphonate therapy (Zometa and Pamidronate) remains an important part of supportive care in minimising the risk of bone fracture and optimising bone health. A/Prof Quach says that some recent data has shown that bisphosphonate therapy every three months may be just as effective as monthly therapy, which has changed how they administer this treatment at her hospital.

‘At St. Vincents we have elected to lengthen the frequency of bisphosphonate therapy to every three months during the COVID-19 pandemic, and will deliver this through the hospital in the home to minimise the number of patients coming into the hospital.’

What is the important information for Myeloma patients to know right now?

Relative to the rest of the world, Australia is in a good position. ‘We have managed to flatten the curve,’ says A/Prof Quach. She says this has allowed hospitals to preserve their inpatient capacity and resources to continue to offer appropriate treatments for patients with blood cancer including multiple myeloma.

‘Non-urgent therapies for multiple myeloma has to now be reconsidered,’ says A/Prof Quach. However, as the situation of the COVID-19 pandemic is still evolving, patient treatments should still be considered case-by-case, taking into consideration hospital capacity and the risk to patients if certain myeloma treatments were to be omitted or delayed for a prolonged period of time says A/Prof Quach.

A/Prof Quach says that patients that were previously denied treatment due to COVID-19 can now start to ask their haematologists to re-evaluate their position to see if treatment can restart. ‘If a patient has been instructed to not have treatment it would be worth asking your doctor again regarding their treatment plan.’

Lastly, A/Prof Quach recommends that patients keep in regular contact with their doctor for treatment plans as the COVID-19 situation is constantly evolving.

28/04/2020
by Mackenzie Gignac

Hodgkin Lymphoma is one of the more rare types of Lymphomas. To learn more about this form of blood cancer we chatted with Associate Professor Ali Bazargan who is a specialist in treating blood cancers.

What is Hodgkin Lymphoma?

Hodgkin Lymphoma is a type of blood cancer that starts in the white blood cells called lymphocytes. HL will begin to grow at one lymph node and spread to other places in the body.

Often the first sign of Hodgkin Lymphoma is found in the neck says A/Prof Bazargan. This form of lymphoma can disperse from one group of lymph nodes to another via the lymphatic system. Additionally, it can spread to other lymph tissues such as the spleen and bone marrow. Because of this sometimes Hodgkin Lymphoma appears in several parts of the body at the same time. It can even spread outside the lymphatic system to form a tumour in other organs, such as the liver or lung. These cases are known as extranodal disease.

Is Hodgkin Lymphoma Curable?

There is good news for those that receive a Hodgkins Lymphoma diagnosis. This type of cancer is curable in more than 75 percent of patients says A/Prof Bazargan. However, there can be therapy-related complications. Sometimes second cancers and cardiovascular disease can cause morbidity and mortality among Hodgkin Lymphoma survivors. These issues might not be apparent until some years after treatment.

How will Hodgkin Lymphoma impact my life?

There are some impacts that patients should be aware of in regards to Hodgkin Lymphoma. Hodgkin Lymphoma and the treatment options can lead to significant fatigue, a low immune system and complicating other medical and psychological issues.

A/Prof Bazargan advises making lifestyle changes that might not directly affect the cancer itself but can play an important role in one’s overall physical and mental health. His recommended guidelines include:

  • Quitting smoking
  • Reduce risk of infection
  • Make dietary changes
  • Exercise regularly
  • Manage fatigue
  • Seek medical or psychological support

These actions can lead to health benefits such as:

  • To help to manage or lessen the side effects of treatment
  • Keeps your immune system strong to aid in the fight against Hodgkin Lymphoma or other illnesses
  • Improves emotional outlook throughout diagnosis and treatment for Hodgkin Lymphoma
  • Decreases the risk of other medical problems that could complicate your health

Another way in which Hodgkin Lymphoma diagnosis might impact your life is through the side effects of chemotherapy treatment. Ali mentions, ‘common side effects of selected chemotherapies include infections, a drop in blood count, anaemia (lack of red blood cells), neutropenia (low white cell count), a drop in platelet counts, hair loss, mouth ulcers, skin rash and diarrhea.

Further, there are some specific side effects that can come of chemotherapy treatment which include: lung toxicity, nerve damage (peripheral neuropathy) which cause pins and needles and numbness in the hands and feet.

What does treatment look like for Hodgkin Lymphoma? How long does treatment take?

The choice of treatment for Hodgkin Lymphoma is determined depending on stage of the disease and prognostic factors. Hodgkin Lymphoma is grouped into three different stages

  • Early-stage favourable risk
  • Early-stage unfavourable risk group
  • Advanced stage Hodgkin Lymphoma

For early-stage favourable risk group treatment will include 2-3 limited cycles of chemotherapy followed by radiation therapy to the field.

For the advanced stage Hodgkin Lymphoma there are two common types of chemotherapy used: ABVD or Escalated BEACOPP which provide a complete remission rate of 80-90 percent.

Both options are comprised of various chemotherapy drugs that combine to provide a synergistic impact on the cancer.

For patients that have relapsed with Hodgkin Lymphoma there are some clinical trial options that use different drugs besides your traditional chemotherapy drug agents.

What are the clinical trial options for Hodgkin Lymphoma?

A/Prof Bazargan says that some clinical trial options now are working to improve the current chemotherapy treatment. ‘Our clinical trials are focused on adding novel agents to the chemotherapy backbone to improve the outcome for patients with newly diagnosed Hodgkin Lymphoma,’ he said.

One of the most recent advances to aid the current chemotherapy treatment is CART therapy. ‘Recent data on CART cell therapy for relapsed Hodgkin Lymphoma has been promising,’ he said. ‘We should see initiation of those successful trials in the near future in Australia.’

Doctors are aware of the long term effects that patients suffer from traditional chemotherapy which can include increased cardiovascular risks, secondary malignancies, infertility, thyroid issues and psychosocial issues.

However, there is progress that is being made on the medical front to reduce these issues through clinical trials. A/Prof Bazargan mentions, ‘further trails are being focused on omitting some of the chemotherapy drugs in order to reduce toxicities, but without impacting the efficacy of planned treatment.’

‘We have seen a number of new treatment options including Brentuximab Vedotin and Pembrolizumab which are currently available through Medicare for relapsed Hodgkin Lymphoma,’ he said. ‘These therapies have changed the horizon for treatment of Hodgkin Lymphoma.’

What Causes Hodgkin Lymphoma?

Hodgkin Lymphoma is caused by a mutation in the DNA of B Lymphocytes which are a type of white blood cells. However, the exact reason for this is not known.

A/Prof Bazargan says that HL isn’t infectious and is also not thought to run in families unless you have a first-degree relative has had lymphoma. In this case your chances are increased, but it is not clear if this is because of inherited genetics or lifestyle factors.

Hodgkin Lymphoma can occur at any age, however most cases are diagnosed in people who are in their early 20s or 70s and it is slightly more common in men than women.

For any patients looking for a second opinion or to talk with a doctor about their recent diagnosis reach out to our team of blood specialists today. Appointments can be scheduled through our office with a doctor’s referral.

28/04/2020
by Mackenzie Gignac

27 APRIL 2020

What is happening with case numbers in Victoria?

The past two weeks have seen a pleasing reduction of case numbers in Victoria, and more broadly across Australia, with only a few new cases diagnosed each day. This is undoubtedly due to the effective social distancing measures. Australia is among very few countries in the world that managed to achieve this. We are indeed the “Lucky Country” in that social distancing measures came in just before widespread community infections occurred.

If we are very very lucky, COVID-19 may in fact disappear from our community, and as long as we keep our borders water-tight, we may be able to get back to a form of “normal life”, albeit without overseas travel or visitors.

The litmus test is whether our case numbers will go up once the current social isolation measures are relaxed. Unfortunately, any effect of interventions being tightened or relaxed will take two weeks to reflect on the case numbers, so “slow and cautious” is the way to go.

How common is asymptomatic infection?

This is very important as although we are diagnosing patients with COVID-19 infection and obvious symptoms, we do not know how many people out there have “silent” infection, who are still dangerous as they can spread the virus without knowledge.

In this regard, a study conducted in Iceland that was reported in the New England Journal of Medicine sheds some insight. Population screening for COVID-19 in Iceland tested 6% of the country’s population; among the 13,080 tests conducted randomly in apparently “normal” people, 100 (0.8%) tested positive for COVID-19. That means one in every 132 “normal” people walking around the streets was infected with COVID-19 without knowledge. In retrospect, around 50% of these people did have some symptoms – such as cough or runny nose.

Interestingly, the Icelandic population testing also included 848 children under 10 years old. Among this large population of children, none were positive. This observation adds to the accumulating data showing not only that children who get COVID-19 have minimal symptoms, it seems like they are less likely to get infected at all. Nobody knows why.

What precautions should I take?

Victoria is about to embark on large scale testing to find out exactly how many “normal” people walking on the streets are in fact infected. Until we know the hard data, our previous recommendations regarding precautions apply.

If for whatever reason you cannot stay at home, and need to mingle in the community, the new “COVIDSafe” app is a good idea as it allows early notification if you have been in close contact with people who may later test positive for COVID-19.

Stay Safe Everybody

Professor Con Tam, Associate Professor Ali Bazargan, Associate Professor Hang Quach, Dr ShuhYing Tan, Dr Matthew Ku and all the staff from Melbourne Blood Specialists.

21/04/2020
by Mackenzie Gignac

21 April 2020

A lot has happened in two weeks. We would like to update you on the latest developments regarding the COVID-19 pandemic.

Case Numbers in Australia are Falling

In an unexpected and pleasant development, the growth rates in case numbers in Australia are falling, proving that social distancing is effective. There are very few countries in the world that managed to achieve this. With the “flattening of the curve”, the peak infection is now expected to occur in September, and hopefully, the case numbers at that time will be within our capacity to provide intensive care and ventilation to all patients who require such care. A major reason for the catastrophic death numbers coming out of Italy and Spain is because the number of patients who required ventilation far outstripped their hospitals’ ability to provide it, thus leading to the death of thousands of patients who would otherwise be saved had the hospitals not been overwhelmed.

The Problem is that the Endgame is a Long Way Away

The current restrictions are working well, but case numbers will skyrocket if they are relaxed. Therefore, we are likely to be facing many months of restrictions and general “lockdown” until one of the following occurs:

1. A vaccine is developed.

There is a massive effort to develop the COVID-19 vaccine but even the most optimistic timelines do not expect the arrival of an effective vaccine for at least 12 months. The old tuberculosis vaccine (BCG) has been resurrected from the archives and is currently being tested on health workers to see if it may boost non-specific immunity to COVID-19; even if successful, BCG vaccination will not be the solution for the majority of the general population.

2. Herd immunity is developed.

That is, a sufficient number of the healthy Australian population is infected and develops immunity to COVID-19. Once approximately 50 – 80% of the healthy population has been infected with COVID-19 and became immune to the virus, the virus will likely die out as it runs out of susceptible patients to infect. Based on current projections, this will not occur until mid 2021.

3. We get lucky and the case numbers get low enough that the virus extinguishes itself in the community.

This is a very unlikely scenario. However, if it happens, and we manage to keep our borders closed until the vaccine arrives, we can potentially get back to near-normal life in about 3 to 6 months. Once again, this is a very unlikely scenario, and will almost certainly require further tightening of current restrictions.

What About Anti-Viral Drugs?

There is no drug that is proven to be effective in patients with COVID-19 infection. Many drugs show promising activity in the laboratory, but very few of these will be expected to actually work in humans.

1. Lopinavir-Ritonavir

The first attempt at anti-viral therapy came out of China, testing Lopinavir-Ritonavir vs no antiviral therapy in patients with COVID-19 infection (the LOTUS study). Lopinavir is a drug used in the treatment of HIV that showed promising activity in the laboratory against SARS, MERS and COVID-19. Unfortunately, this well conducted study showed that Lopinavir did not work at all in humans with COVID-19 infection, with no improvement in the virus count or the chances of surviving the infection.

2. Hydroxychloroquine (Plaquenil)

The second “anti-viral” drug is one that has been highly advertised by Donald Trump – the old anti-malarial drug Hydroxychloroquine. Some of you may be taking this drug already as it is commonly used to treat joint and skin conditions; you may also find it hard to get this drug at the pharmacy as many people have taken Donald Trump’s advice and stockpiled Hydroxychloroquine, leading to a global shortage. So does Hydroxychloroquine work?

Well, firstly, it is not directly toxic to the virus. Rather, it may modify normal cells in the human body so that it becomes more difficult for viruses to attach to and grow within our bodies. Experiments conducted in animals with other viruses have been failures, variously showing either improvement or worsening of infection with Hydroxychloroquine or chloroquine therapy. Specific to COVID-19 infections in humans, the data is very poor quality, and all we know thus far is that the drug is most definitely not a game-changer.

3. Remdesivir

The hottest drug on the scene at the moment is Remdesivir, an experimental anti-viral drug made by Gilead Sciences that blocks a class of enzymes (called viral RNA polymerases) within viruses like Ebola, SARS, MERS and COVID-19. On April 10th, the New England Journal of Medicine published a report on 61 patients with moderate or severe COVID-19 infection who were given Remdesivir on a compassionate basis (i.e. in desperation and outside of a properly conducted and controlled clinical trial). This was given as a daily infusion through the veins for 10 days.

The group of most interest in this report was the 34 patients who were so sick, they were on ventilators when Remdesivir was started. Of these critically unwell patients, 56% got better, 26% remained the same, and 18% died despite experimental anti-viral treatment. Is this a good outcome? The chance of death for these types of patients in reports from China and other countries range widely between 17% to 78%. So one can argue that the death rate seen so far in patients receiving Remdesivir is at the lower end of expected, at 18%. However, this rate will definitely rise if one remembers that many of the patients who remain alive, but without improvement, will likely die eventually. In conclusion, Remdesivir is not a game-changer, and either does not work, or improves the chances of surviving COVID-19 marginally at best.

Caution is Still the Key

Prevention is still the best way to approach the current COVID-19 crisis.

Remember, probably at least half of young people infected with COVID-19 have minimal or no symptoms, so be cautious with anyone you meet, and take universal precautions.

Stay safe, everybody.

Professor Con Tam, Associate Professor Ali Bazargan, Associate Professor Hang Quach, Dr ShuhYing Tan, Dr Matthew Ku and all the staff from Melbourne Blood Specialists.

Diffuse Large B Cell Lymphoma (DLBCL) is a common fast-growing lymphoma. Such a diagnosis often comes as a shock to patients. We spoke with St Vincent’s Hospital Clinical and Laboratory Haematologist Dr Matthew Ku to understand and learn more about DLBCL, how it can impact patients’ lives, what routine tests are conducted, what treatment options are available and the potential underlying causes.

What is Diffuse Large B Cell Lymphoma?

Lymphomas are blood cancers that can affect lymph glands, blood and other organs. Lymphomas can be subdivided into Hodgkin and Non-Hodgkin Lymphomas and DLBCL is an aggressive form of Non-Hodgkin Lymphoma. It is the most common type of lymphoma and accounts for 30 percent of all lymphomas, says Dr. Matthew Ku.

Although a cancer diagnosis is always worrisome, DLBCL is a curable cancer. Dr. Ku says patients recently diagnosed with DLBCL should stay positive. ‘DLBCL has a good chance of responding to therapy with the chance of a cure at 50 to 60 percent, which is better than most cancers.’

Dr. Ku gives hope to patients that have been diagnosed with DLBCL. ‘If you are managed by an experienced haematologist then you are in good hands, since there are proven therapies that are effective.’

Will the DLBCL diagnosis impact my life?

Dr. Ku says unfortunately, there will be a short to medium impact on the life of a patient that has been diagnosed with DLBCL. There are two primary areas affected: psychosocial and physical

  1. Psychosocial Impact

After the initial diagnosis, patients can undergo a period of anxiety, grief and disbelief upon receiving the news. The news of a cancer diagnosis tends to have a psychological effect on the patients themself as well as their families and friends.

Dr Ku says patients should be encouraged to know that they are not alone, and that support is available for them to help alleviate psychological stress. Most tertiary hospitals offer psycho-oncology which provide counseling to cancer patients and their families. Additionally, Dr Ku advises that there are family and social support options through social work, as well as external support through third-party organisations, such as theLeukemia Foundation.

The social impact of a DLBCL diagnosis might also cause disruption to the patients’ studies or employment. ‘I tell my patients not to be too stoic, and try to take some time off to see how they go with chemotherapy.’

  1. Physical Effects

Dr. Ku says there are two ways the diagnosis of DLBCL could exert physical impact on the patients. The first is how DLBCL directly affects the body. DLBCL could cause symptoms such as enlarged lymph nodes, fevers, significant night sweats and weight loss (>10% in body weight).

The second way is how the therapy for DLBCL could negatively impact the patients. The most common chemotherapy used for the treatment of DLBCL is RCHOP. RCHOP combines a variety of drugs that are usually given every 21 days. Dr Ku says while some patients don’t have significant side effects with chemotherapy, many do develop side effects and haematologists can’t always predict how everyone will react to chemotherapy. There are some side effects that patients might encounter with chemotherapy including hair loss, nerve irritation or damage (neuropathy), low blood cell counts or low immunity, fertility issues, and reduced heart function, especially in the elderly patients. For this reason, patients receiving RCHOP chemotherapy should have their heart function tested before and possibly during chemotherapy.

What are my treatment options for DLBCL?

DLBCL is a curable lymphoma and the standard first line of therapy is RCHOP chemotherapy. ‘RCHOP chemotherapy has been shown to be the most effective first line treatment for DLBCL,’ says Dr. Ku. ‘There have been many studies that tried to improve RCHOP but RCHOP is still the best at the moment.’

Many patients respond well to RCHOP treatment. However, for those patients that do not respond and progress or relapse later, their next option is salvage therapy followed by stem cell (‘bone marrow”) transplant. ‘However, many patients don’t go into remission and they don’t make it to stem cell transplant,’ says Dr Ku. In that situation, clinical trials are offered as the next line of treatment.

Dr. Ku says that the length of chemotherapy treatment depends on the “stage” of the DLBCL.

Early stage DLBCL might require three to four cycles of RCHOP chemotherapy, possibly followed by radiation treatment. As RCHOP is given every 21 days, this would be around three months of chemotherapy for those in stage I-II.

The more advanced stage (III-IV) DLBCL usually requires six cycles of RCHOP chemotherapy, which will be around four to five months of treatment.

What tests can I expect for DLBCL?

When a patient is diagnosed with DLBCL there are tests that we do to further characterise the disease, and to assess a patient’s suitability for chemotherapy.

‘We do a baseline set of blood tests including full blood count, kidney function, liver function, calcium, magnesium, phosphate, LDH, Hepatitis B & C, and HIV.” Investigations such as PET/CT scans, as well as a bone marrow biopsy are also routinely performed to assess the “stage,” or the extent of DLBCL involvement. Dr. Ku explains, ‘PET scan measures the disease burden of DLBCL. Sometimes we do a bone marrow biopsy to see if the bone marrow is affected.’

What causes DLBCL?

Dr. Ku says most DLBCL can’t be traced back to a cause. If you have a first-degree relative with a blood cancer there is an increased chance. Additionally, some substances have been reported to be linked to higher rates of lymphoma, such as the weed pesticide RoundUp. However, for the majority of patients, unfortunately lymphoma occurs without a clear cause.

Are there any actions being taken by Melbourne Doctors to advance the care of patients now and for the future?

‘There is significant cooperation and collaboration among haematologists within the country to come up with ideas and strategies that can improve the outlook of our patients,’ says Dr. Ku.

The ALLG (Australasian Leukaemia and Lymphoma Group) and ALA (Australasian Lymphoma Alliance) gather lymphoma specialists from Australia and New Zealand to come up with new ideas to manage patients with DLBCL.

‘We are collecting data to see how we can improve the way future patients are treated and managed,’ says Dr. Ku.

Dr. Ku emphasizes that retrospective studies that work through big cooperative groups are very important to advance patient care.

The state of medicine is constantly evolving. While chemotherapy is one of the most common methods to treat cancer, medical experts of today are looking towards clinical trials to improve outcomes for those diagnosed with cancer.

What are clinical trials? Haematologist and disease group lead at Peter MacCallum Cancer Centre Professor Constantine Tam offers some clarity on the topic of clinical trials.

‘Clinical trials used to study new combinations of chemotherapy in patients to see if they work better or are less toxic than old combinations,’ says Professor Tam. Fast forward to today and the clinical trials have moved from testing chemotherapy options to less toxic oral drugs. ‘We have the present age where we are testing new forms of drugs which target specific vulnerabilities of cancer,’ says Professor Tam.

What is the difference between traditional chemotherapy treatment and new clinical trials? Chemotherapy targets and damages all DNA - good or bad.

‘These drugs are very precise, unlike chemotherapy.’ says Professor Tam. ‘Chemotherapy damages the DNA in all our cells, cancer or not, in a random manner.’

To compare the two treatment methods Professor Tam gives an analogy, ‘chemotherapy is like a shotgun, hitting and hurting everything in its way. The new targeted drugs are precision rifles.’

The future of these new cancer treatments can have great applications for those battling cancer.

Lina Pennisi is a mother of two and was first diagnosed with Non-Hodgkins Lymphoma in 2007.

‘I couldn’t believe what was happening,’ said Lina recalling the news about receiving her diagnosis. ‘Life is not going to be the same for me anymore.’

Lina went through chemotherapy treatment in December 2007. Although the treatment was successful, it was a difficult experience for Lina, ‘I do not wish chemotherapy on my worst enemy with what I went through.’

Lina met Professor Tam in 2010 where she first started giving clinical trials a shot. Lina had trust in Professor Tam, ‘I knew he wouldn’t suggest a study trial if he didn’t think I could cope with it,’ she said.

Lina mentioned she had already been through the worst so she wanted to explore other options. ‘When chemotherapy was mentioned I almost had an anxiety attack,’ she said. ‘If the first study trial didn’t work, I would have tried the second study trial.’

Like any treatment, clinical trials can’t guarantee a good outcome. However, these trials are recommended by doctors looking to make treatment advancements for their patients. ‘Clinical trials are designed by specialists who are experts in their fields, in order to do what these experts think will most likely improve current treatment,’ says Professor Tam.

In 2016 she agreed to a clinical trial with a new class of drugs, BTK inhibitors, and which have been successful. ‘I recommend anyone that’s going through a tough time to one, get a second opinion, and two, try a study trial,’ says Lina. ‘Once I got the information I thought this is right for me.’

Lina’s said her family was her main motivation throughout her cancer treatment rounds.

My children really were my drive to get better,’ said Lina upon receiving her diagnosis. ‘I am going to fight for my future, not for myself but for my family.’

Lina stayed strong throughout her fight with cancer so she could raise her children. ‘I want to be there when they get their license, get married, and become a grandmother,’ she said holding back some tears. ‘I just want to be there for them.’

The most recent test results from Lina’s clinical trial treatment have been a success. For the first time in 13 years her CT scans showed no results of Lymphoma.

‘I never had a CT scan showing such great results, which made me quite emotional,’ she said. ‘This is the best I’ve felt in 13 years.’

Lina offers some advice for anyone that has recently been diagnosed or currently going through treatment.

‘Stay strong and leave yourself open to anything. Have trust with the great doctors and knowledge we have.’

Lina’s story can offer some hope for those diagnosed. Blood cancer patients can look forward to treatments offered today and new treatments that are being developed for the future.

07/04/2020
by Mackenzie Gignac

Our team at Melbourne Blood Specialists is committed to the health and safety of our patients. The evolving COVID-19 outbreak is being monitored closely by our team of healthcare professionals as we continue to work to provide the best treatment options for our patients.

Our office will remain open, however, with patient safety in mind new limitations have been enacted. All further consultations will be conducted by phone. In exceptional cases physical consultations can still occur, but only when a physical examination is critical.

New precautions are set in place for any patient visiting our office. You will be asked to wash your hands before entering with soap and water or alcohol-based hand sanitizer. Additionally, we ask that if patients need support from a family or friend for a physical appointment that they only bring one other guest to follow social distancing guidelines.

Patients should not attend our office and should self-isolate if:

  1. You are experiencing any symptoms of COVID-19 including:

  2. Cough

  3. Sore throat
  4. Fever
  5. Fatigue
  6. Shortness of breath

  7. Have been in contact with someone that has tested positive or has risk factors for COVID-19 such as overseas travel in the past two weeks

How does COVID-19 affect my cancer treatment?

If you are a patient and you have been diagnosed with COVID-19, please let us know ASAP so we can reassess your treatment plan.

For any patients that might test positive for COVID-19:

  • If you have been on stable oral drug treatment for at least 3 months and have been doing well with your cancer under control, our doctors ask that you stop your cancer treatment until you fully recover from COVID-19.
  • For patients receiving intravenous chemotherapy treatment, please contact us to speak with your doctor to determine how COVID-19 affects your medical care plan.
  • In all cases, please contact our office ASAP to let us know about your COVID-19 diagnosis.

How does COVID-19 affect people with blood cancers?

If you have Leukaemia, Lymphoma or Myeloma, you are not at a greater risk of contracting COVID-19 than others. However, having a blood cancer weakens the body’s immune system which does put you at a higher risk of developing more severe symptoms than someone who is healthy.

What can I do to stay safe?:

  • The best way to stay safe is by avoiding exposure to the virus and staying at home unless necessary
  • Practice good hand hygiene by washing your hands frequently with soap and water or cleaning your hands with at least 60% alcohol-based hand sanitizer
  • Do not touch your face, eyes, nose, and mouth
  • Ensure you cover your mouth and sneezes with a tissue or into your elbow when you are sneezing or coughing
  • Avoid close contact and maintain 2 meters or 6 feet of distance between yourself and other people
  • Clean and disinfect your home and other frequently touched surfaces such as phones, keys, laptops, and doorknobs
  • We also recommend that you contact your local GP or pharmacist and receive the influenza vaccination as soon as possible.

Should I wear a face mask out in public?

There is increasing data that wearing of masks may reduce the risk of COVID-19 transmission. The highest protection comes from specialist N95 or P2 masks, followed by surgical masks. However, these masks are difficult to purchase as they are required for the protection of doctors and nurses in hospitals treating infected patients.

Simple cloth masks or other face-covering materials do assist in reducing the risk of droplet transmission, and we recommend all our patients wear them whenever they are outside their home. Be sure to wash them often (preferably in water at 60 degrees Celsius or hotter) to keep them clean.

The CDC demonstrates how you can make your own face covering for your safety during the COVID-19 outbreak here.

COVID-19 Resources for further information

New information of COVID-19 is frequently evolving day-by-day. We recommend checking in on these sources to review coronavirus public health advice news.

At Melbourne Blood Specialists health and safety of our patients is our top priority. Our team is here to stand by you when you are not feeling well. Our team will still work to continue to serve our patients with the highest standard of medical care during these times.

A Very Happy Easter to all our Patients. We hope that you managed to spend time with your loved ones, even if this is by Facetime or Zoom.