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.’
There are four main immunotherapy strategies currently available according to Dr. Ku.
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.
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.
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.
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.
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.
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.’
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.
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.
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.
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.
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:
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:
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.
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.
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:
Chemotherapy or disease modifying therapy options may be available for patients with advanced MDS. Some of these options include:
Azacitdine or Vidaza is given as an injection under the skin for seven days every month.
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.
Lenalidomide or Revlimid is a tablet treatment used specifically for patients with 5q-syndrome subtype of MDS.
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:
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.
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.’
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?
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.
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.
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.
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:
‘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.’
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.
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.
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.’
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.
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.
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.
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.
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:
These actions can lead to health benefits such as:
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.
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
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.
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.’
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.
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.
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.
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.
A lot has happened in two weeks. We would like to update you on the latest developments regarding the COVID-19 pandemic.
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 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:
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.
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.
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.
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.
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.
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.
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.
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
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.’
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.
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:
You are experiencing any symptoms of COVID-19 including:
Shortness of breath
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
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 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.
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.
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.