Magrolimab – potential new treatment for newly diagnosed MDS
A ‘first-in-class’ therapy that recently received FDA Breakthrough Therapy designation in the U.S. for the treatment of newly diagnosed MDS will be available “very soon” to Australians in a clinical trial.
Magrolimab is an investigational anti-CD47 monoclonal antibody that is being studied in the randomised Phase III ENHANCE study which is evaluating the safety and efficacy of magrolimab in combination with azacitidine (Vidaza®) in higher risk MDS.
Professor Andrew Wei, haematologist at the Alfred Hospital (Melbourne), said magrolimab “was a potential important advance for patients with MDS” and “a treatment option with a highly novel mechanism of action”.
“Magrolimab activates specialised immune cells to recognise, engulf, and digest malignant cells,” with response rates in single arm early-phase trials “that are very promising”.
“Randomised clinical trial validation is now the next step,” said Dr Wei.
Dr Wei is on the global steering committee for the randomised studies in MDS and AML (in which magrolimab also has shown activity in poor risk patients) and is the principal investigator for the ENHANCE registration trial which is in the process of opening in hospitals across Australia.
The Alfred has just commenced recruitment for the trial, with other sites coming online over the next few months.
This means most eligible newly diagnosed patients with higher risk MDS should be able to access the trial “as long as they pass eligibility assessments”.
“There are other studies in this area as well, such as venetoclax plus azacitidine, which is also open to recruitment to patients with newly diagnosed MDS. The field has never been so active,” said Dr Wei.
Clinical haematologist, Professor Steven Lane, who heads a research laboratory at QIMR Berghofer Medical Research Institute (Brisbane) and whose focus is on myeloid disorders including MDS, has described magrolimab as “a super exciting drug”.
Dr Heshaam Mir, Medical Director Australia & New Zealand, Gilead Sciences, which has developed the drug, said, “magrolimab represents an alternative treatment for those patients with limited options”.
“But it is important to remember it is still an investigational medicine whose safety, efficacy, and clinical benefit have yet to be established.
“Magrolimab is not yet licensed or approved for any use by any regulatory authority.”
The FDA granted Breakthrough Therapy designation for magrolimab based on the positive results of an ongoing Phase Ib study, evaluating magrolimab in combination with azacitidine in previously untreated intermediate, high, and very high-risk MDS and AML.
In data presented at the 2020 European Hematology Society Congress, 91 per cent of evaluable MDS patients treated with magrolimab plus azacitidine achieved an objective response, with 42 per cent achieving a complete remission. The combination of magrolimab plus azacitidine was generally well-tolerated. No maximum tolerated dose was reached and no MDS patients discontinued treatment due to a treatment-related adverse event.
Breakthrough Therapy designation is designed to expedite the development and regulatory review of investigational treatments for serious or life-threatening conditions that, based on preliminary clinical evidence, have the potential to substantially improve clinical outcomes compared with available therapy.
“The Breakthrough Therapy designation recognises the potential for magrolimab to help address a significant unmet medical need for people with MDS,” said Dr Merdad Parsey, Chief Medical Officer, Gilead Sciences.
Magrolimab is a monoclonal antibody against CD47, a protein that works as a ‘don’t eat me’ signal used by cancer cells to avoid being ingested by macrophages — a kind of immune cell that engulfs invaders.
The investigative therapy works in a similar way to checkpoint inhibitors, but instead of activating T-cells, it improves the ability of macrophages to identify and eliminate cancer cells.
Because this evading mechanism is used by several cancer types, magrolimab represents a promising approach for a wide range of solid and blood cancers. Magrolimab has already received fast track status for diffuse large B-cell lymphoma and follicular lymphoma.
Speak to your haematologist regarding your eligibility and referral to the trial. For further information, contact the Alfred Hospital trial manager, Nola Kennedy, on ph: 03 9076 2217 or email: firstname.lastname@example.org
Familial research key to blood cancer prevention strategy
The Australian Familial Haematological Cancer Study (AFHCS) leads the world in the field and has a research cohort of more than 200 families with a history of blood cancer.
The AFHCS was initiated in 2004 by Adelaide geneticist, Professor Hamish Scott. Prior to this, it was recognised that blood cancers did run in some families, but very few of the gene mutations that cause this to occur were known.
Prof. Scott and Dr Anna Brown, who was working collaboratively with him in another lab, started studying a few families.
“Of course, as soon as people realise you’re studying genetics, they come to you with their stories,” said Dr Brown, Head, Molecular Oncology in the Department of Genetics and Molecular Pathology at SA Pathology (Adelaide).
Enrolling patients in the study
A framework was developed for haematologists with patients where MDS, AML or other blood cancers ran in their family, to enrol them in the research study, which started looking into the gene changes underlying these family’s histories.
“We have one of the longest running familial blood cancer studies in the world. It’s a systematic study to find answers for these families,” said Dr Brown.
“Over 200 families are enrolled and because there are multiple family members with all kinds of different blood cancers, or carrying a mutation, we’ve got thousands of individuals across the families we are studying.
“We have very good relationships with haematologists all over Australia.”
Most referrals to the AFHCS come from haematologists treating a family member with a blood disorder/blood cancer whose medical history showed a strong family history of the condition. Information about the study was then given to the patient, via their haematologist, to see if the patient was interested in participating in the research.
“If they are, a research nurse then contacts a family member for more information and to give more information about the study. If they want to go ahead, the research study consenting process is started.
“The study coordinator normally starts with one family member and gets a family history, then sequentially contacts other family members who are interested in participating as well,” said Dr Brown.
“We build up a very detailed family history, go through their medical background, and if there is blood cancer in their family, collect samples from them for genetic testing.
“All this is done in a research setting and the information is de-identified, so we don’t see names of individuals we are studying.
“Some people are really happy to participate in the research, want to know everything and are really engaged. Others want to help for the betterment of everyone, but don’t necessarily want to know that personal information about themselves,” said Dr Brown.
“We do gene sequencing on family members who have provided material, researching their genomes, to see if we can find a genetic change that’s present in the family members who have reported either a blood disorder or a blood cancer.”
Dr Brown said the AFHCS often gave presentations to organisations, including the Leukaemia Foundation, at their patient education days, “and sometimes individuals contact us directly.”
Familial linkages occur in “pretty much all the different types of blood cancers and disorders to some degree or another”, she said.
“We have MDS and AML, but we also have a lot of lymphoma families, myeloma families, and chronic lymphocytic leukemia. Basically, in every type of blood cancer we can find a family where it seems to be occurring more often than you would expect.
“That suggests that there’s something genetic underlying that.”
In 2016, the World Health Organisation published clinical testing guidelines for familial predisposition to myeloid malignancies.
“As well as our research study, for families with a history of myeloid blood cancers such as MDS and AML, we are part of an international clinical network of experts and our laboratory offers accredited genetic testing that can be ordered through clinical genetics centres and clinical haematologists,” explained Dr Brown.
Why does it seem blood cancer may be occurring more often?
“Diagnosing blood cancers has become a lot better with modern medicine,” said Dr Brown.
“In the past, people might have been affected by leukaemia and passed away without it being diagnosed or identified as the reason they passed away.”
And blood cancer is more visible now.
“If someone younger gets this kind of disease, it stands out more, and makes it easier for us to identify when there is a family history.
“There is some concern that the age of diagnosis of some of the blood cancers is getting younger in more recent generations, and that is something we’re actively researching.
“The field hasn’t done the right studies yet to show whether that’s actually true, but in some cases it seems like it might be.
“That’s something we definitely want to look into – whether other factors are also interacting with the genetic changes in these families, maybe environmental factors, but we don’t know of any at the moment.”
Why familial research is important
“There are benefits in participating in this research,” said Dr Brown.
Information from this research is most important when a family member is looking at having a stem cell transplant or bone marrow transplant as a curative therapy, “because most frequently you’ll look for a family member to be the donor”.
“It is really important to offer genetic testing to these people, to make sure they’re not carrying any mutations that we can identify that might be causing that family history, and to make sure any potential bone marrow donors aren’t carriers of those mutations without realising.
“You don’t want to transplant bone marrow that’s got an inherited mutation. We know that gives you a risk of complications with how well the bone marrow transplant works.
“We’re focusing on identifying carriers of known gene mutations early, and enrolling them in the study, so we can work with their haematologist, to monitor them more closely.
“What we would like to do in our research is figure out ways to stop leukaemia from developing in people who’ve inherited a mutation.”
“A new aspect of the study is looking at why they go from a state of having an inherited mutation, to developing blood cancer. Something else has to happen in between, to trigger that. What is it?
“Can we find out how that happens and find a way to treat at that point? So patients don’t go on to get leukaemia. We’ve got a lot of research projects in that area.
“And having this knowledge, the haematologist knows to keep a really close eye on someone who’s at a greater risk, which allows them to manage their health better,” she said.
Testing a blood cancer prevention strategy
Dr Brown said clinical frameworks were being put in place “to find clever ways to test a leukaemia prevention strategy” because it is being given to a patient who has a gene mutation but is otherwise well, and it may take a longer time to know the answer, and “that’s ethically difficult”.
“We’re still working through the ways in which we could get to the point where we could have a human clinical trial. I don’t think it will be too far away.”
Stopping blood cancer from developing “is absolutely the aim of a lot of the research we are doing right now”, she said.
“The field recently moved from just trying to identify what some of the mutations are, to figuring out a pathway to generate models in the lab and find therapies that might intervene at a much earlier point than waiting for a person to get full-blown leukaemia.
“The main thing for treating someone, to prevent leukaemia, is finding a compound with a good safety tolerability profile, unlike intensive chemotherapy which is used to treat acute myeloid leukaemia.
“You wouldn’t give that to somebody who’s otherwise healthy, because there’re just too many side-effects,” said Dr Brown.
“We’re looking at other agents that might change the blood compartment in ways that relieve some of the stress that the inherited mutation puts on it.
“If we can relieve that stress on blood cells and stem cells, it might reduce the chance that they become leukaemia,” she said.
Christine has a rare genetic predisposition to MDS
Christine (left) and husband Greg (right) at their daughter Ashleigh’s end of year school service in November 2018.
After losing her dad to MDS, and her brother’s diagnosis just a month before hers, Christine Heath’s family underwent genetic testing to understand whether their MDS couldbe hereditary.
Christine, a high school maths teacher, fell suddenly, back in 2015, when walking up the stairs to class, then fainted while lining her students up.
“It was just for a split second and I only dropped my books,” said the now 53-year-old from Port Lincoln, South Australia.
But she thought to herself, “that’s not right”, and went to the doctor to be checked out. Her blood tests returned some “funny results” and her doctor was particularly concerned about her haemoglobin level.
She was given the option of redoing the test in three months or going straight to a specialist.
“Given my dad, Geoff, had died from MDS in 2011, I opted to go to the specialist,” said Christine.
She saw the same haematologist who had treated her father, and he assured her any blood issues could not possibly be hereditary, that it was unlikely to be MDS, but he would monitor her over the coming years.
A ‘double-whammy’ diagnosis
After being closely monitored for several months, Christine was formally diagnosed in April 2016 with myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T)*.
“This was just a month after my older brother, Stephen, who was also going to our dad’s haematologist, received the same diagnosis – a double whammy,” said Christine.
“My daughter, Ashleigh, was in year 10 at the time and I really wanted to be actively involved in her life, see her graduate, and live with my husband, Greg a lot longer.
“To begin with, I was put on ‘watch and wait’ with tissue and blood samples taken to find a stem cell donor.”
Even after her diagnosis, her haematologist was still reluctant to class her MDS as hereditary.
It wasn’t until Christine, Stephen, and their partners attended a Leukaemia Foundation MDS workshop in September 2016 that they started to find some answers.
“The workshop was in Adelaide and there was a geneticist there, Professor Hamish Scott, who we approached after his session, and told him about our situation,” said Christine.
“He said straight away, ‘oh I definitely want your genes… let us do some testing’.”
Another haematologist arranged for samples from Christine and Stephen to be shared with Prof. Scott and extra information about their dad and grandmother was provided.
The researchers asked her mum, Gill, for permission to use Christine’s dad’s blood samples. These had been stored as they looked different, but Geoff’s medical team was unable to understand why at the time.
“My mum also remembered that other family members had experienced blood issues and so they did a family tree and tracked it back a couple of generations,” explained Christine.
“It was then confirmed that we do indeed have a genetic predisposition to MDS!”
Ashleigh also has provided hair and blood samples, but she chose not to ask for information about any findings.
“She said she might when she has a family one day, but right now she’s focused on living for every day and doesn’t want that hanging over her head,” said Christine.
“She has just begun studying science at the University of Adelaide, majoring in immunology and genetics.
“We are really proud of her and the interest she has in the science behind all this. She could be the one who makes a difference for us in the future.”
In October 2016, Christine flew to the Peter MacCallum Cancer Centre in Melbourne to get a second opinion.
“I learnt there that there were no clinical trials suitable for me and to just continue to maintain a balanced diet and consider part-time work.”
Early the following year, Christine needed to begin having blood transfusions and erythropoietin (EPO) injections every two months.
In 2018, as her condition worsened, she stopped work altogether.
“I’ve been on income protection ever since,” she said.
“I strongly encourage people to check whether their super gives them the option.”
Time for transplant
After living with Ashleigh in Adelaide for 12 years while she completed her schooling, Christine moved back to Port Lincoln to be with her husband in early-2019. Greg had stayed at Port Lincoln to support his parents as his father was battling leukaemia at the time.
When Christine’s transfusions got closer and closer together, her haematologist said, ‘time’s up, we’re going to transplant’.
“A sudden drop in two of the blood lines had appeared, which was the marker he was waiting for,” she said.
“I was a bit scared, but I knew that’s what I wanted to do.
“I felt far too young to die and I didn’t want to have to deteriorate like my dad had done before he passed.”
Ashleigh had produced a booklet for her senior school research project on the associated benefits and risks of transplants.
“Her project question was, ‘do the positive outcomes of getting a stem cell transplant to treat blood cancer outweigh the risk factors?’” said Christine.
“She interviewed a number of haematologists, ran a patient survey, and did a heap of research.
“She did an amazing job, and I think it really helped her to understand the process and cope with what I was going through.”
Christine and her family were given the time to take a holiday together before her transplant.
“We went up to Queensland and did ‘the worlds’,” said Christine.
“We were able to visit Ashleigh’s cousins there, and I didn’t want to take the risk of going overseas in case something went wrong.
“It was such a great trip. I’m not a big ride person but I was chief bag holder and took all the photos while they went on the rides.”
On 16 August 2019, Christine had her transplant with stem cells donated from the umbilical cord blood of two baby girls, after a previous donor match was no longer viable due to age.
“When I got to the hospital everything happened very quickly. I was started on chemotherapy and then I had full body radiation.
“On transplant day, I had Greg and my mum there, as well as Stephen and his wife, as he was about to have his own transplant and wanted to see the whole process.
“My niece, Stephen’s daughter, was also there. She had just finished her honours degree in science, supervised by haematologist, Dr David Yeung.
“Shortly after, she was employed to work with the transplant team doing all the data collection for transplant patients and looking for trends in treatment.
“It was feeling a little bit like a party, but it was kind of a letdown as the transplant itself is like having a transfusion.”
Christine needed to stay in hospital for seven weeks after the transplant.
“I consider myself extremely lucky as I didn’t have any long-term issues with graft versus host disease (GVHD) and didn’t go into intensive care once,” she said.
“I did go off my food for a bit and had to have a feeding tube, which I hated. I had a bad reaction to cyclosporine**, and they put me on steroids for suspected GVHD which caused me to develop steroid-induced diabetes.
“That was only temporary for about three months and by the time they had taught me to do the injections myself, it was time to stop.”
Leukaemia Foundation support
Christine and Greg stayed at the Leukaemia Foundation patient and family accommodation village in Adelaide for six months during her transplant and recovery.
“It was really important to stay close to the hospital as Port Lincoln is a seven-hour drive from Adelaide,” said Christine.
“We loved it there and we made quite a few friends around the village. We all kept an eye out for each other.
“There’s morning teas and the staff put on a Christmas lunch for everyone. There’s also a nice little games room where my husband and I would play a bit of ping pong or table tennis when I was feeling better.
“I cannot thank everyone from the Leukaemia Foundation enough – they were brilliant.”
Christine was kept busy during her recovery, with regular appointments and blood tests.
“These were weekly to begin with, then steadily decreased to fortnightly and monthly appointments,” said Christine.
“I also had lots of physio to build my muscle as I had lost about 15 kilos while in hospital.”
Although the Heaths had hoped to return home in February 2020, the COVID-19 outbreak meant they had to remain in Adelaide until the situation stabilised.
“I actually think I would’ve struggled being away from a major hospital during that time. You want that peace-of-mind that help is just down the road should you need it,” she said.
Focused on the future
Eventually returning to Port Lincoln in April 2020, Christine has been focusing on slowly settling back into everyday life.
“Life is looking really good and I’m now even talking about when I can return to work,” she said.
“I try to exercise every day and do what housework I can. I keep busy with people dropping in, and I’m really looking forward to summer so I can get back to the beach.
“But I’m always conscious of not overdoing it as I can still get really tired some days.”
Christine has regular tele-health appointments with her haematologist and travels back to Adelaide every two months for a face-to-face check-up.
“I can have my blood tests in Port Lincoln and I need to have a venesection fortnightly because my iron levels are too high from all the transfusions,” explained Christine.
“I also have an immunoglobulin infusion once a week which is a subcutaneous injection, two little needles into my stomach which I’ve been taught to self-administer.”
Now she is firmly focused on living for every day and is confident that with medical advancements, outcomes for people with genetic diseases will improve.
“I’m still in contact with Prof. Scott and serve as a consumer advocate whenever the opportunity arises,” said Christine, who together with two other women, started an MDS/MPN-RS-T Facebook support group.
“I also want to stress that our family is an extremely rare case and MDS is not typically a hereditary disease,” said Christine.
*MDS/MPN-RS-T is a rare subtype of MDS/MPN characterised by anaemia, bone marrow dysplasia with ring sideroblasts and persistent thrombocytosis ≥450 × 109/L with proliferation of large and morphologically atypical megakaryocytes.
**Cyclosporine is an immunosuppressant used to prevent rejection, following allogeneic bone marrow transplantation.
MDS-survivor, Danny now dedicated to raising awareness
This MDS World Awareness Day, Danny Palmer will celebrate achieving remission after undergoing a life-saving transplant earlier this year. He’s now committed to raising awareness of the many different blood cancers, encouraging others to donate blood and plasma, as well as fundraise in support of the community.
“I just assumed I was working too hard – I maintain parks and recreation areas for the local council and was walking a lot of kilometers every day,” said the 50-year-old who lives on the Gold Coast in Queensland.
“I have type-1 diabetes and bipolar disorder as well, so I was in regular contact with my doctor.
“I had an appointment in August 2019 and told him what was going on, he said, ‘you’re due for a blood test for your diabetes anyway but I think there’s a bit more to this’.”
“Low and behold, when the results came back it looked like I had leukaemia.”
Danny was taken to the local Gold Coast Hospital where he received a blood transfusion and underwent further tests.
“It was then confirmed that I actually had high-risk MDS. I was told it was a blood cancer, but I had no idea that there were any other types than leukaemia,” said Danny.
“It was a steep learning curve, and I was pretty scared.”
Danny was put on a drug called azacitidine, a daily injection for a week every four weeks, and was given only eight months to live.
“My case was then submitted to the Royal Brisbane and Women’s Hospital (RBWH) board as an ideal candidate for a transplant,” said Danny.
“My haematologist at Gold Coast Hospital has a great relationship with my now haematologist in Brisbane, Dr Siok Tey.
“I was really lucky that I didn’t have to go the roundabout way to get to transplant but I was put forward to the right people from the outset.
“They assess a lot of things like your survival chances, any comorbidities, your age and the progression of your disease.
“In the new year I was told I had been accepted but that I would need a 10/10 perfect-match donor.”
Both Danny’s sister and brother were not a match, so the search was widened to find an unrelated donor.
“They first found a perfect-match donor from Germany; however, the COVID-19 pandemic had just hit, and we were told no more stem cells were making it into the country,” explained Danny.
“We were back to the drawing board for a while there. Thankfully, another 10/10 match was soon found down in Victoria and I was all set to go in April.”
On 2 April 2020, Danny underwent the transplant in Brisbane spending a total of 24 days in hospital.
Basit Salik, Dr Jamie Kuzich and Dr Julian Grabek have been named the successful recipients of the 2021 round of PhD Scholarships to support their work on projects to improve understanding and treatment for Acute Myeloid Leukaemia (AML) and Myeloproliferative Neoplasms (MPN).
AML is an aggressive blood cancer with an average 5-year survival rate of 28% and low rates of long-term survival. Whilst most patients appear to achieve a remission with current treatment, the majority eventually relapse.
Currently 1,122 people are diagnosed with AML each year in Australia and sadly, 1,111 Australians lose their life to the disease annually. Alarmingly, these figures are projected to grow to reach 3,722 people diagnosed per year and 2,847 dying from the disease each year by 2035.
MPNs occur when bone marrow stem cells grow and reproduce abnormally. In patients with MPN, abnormal stem cells produce excess numbers of one or more types of blood cells (red cells, white cells and/or platelets). These abnormal cells cannot function properly and can cause serious health problems unless properly treated and controlled.
People with MPN have an increased risk of the disease transforming to an acute leukaemia depending on the subtype – essential thrombocythaemia (4%) Polycythaemia vera (9%) and myelofibrosis (21%).
“Research is a crucial tool to improve blood cancer survival rates and ensure Australians can live well with their diagnosis, and while these reports show us that significant gains have been made in this area, they also show is that there is more work to be done to reduce mortality and associated economic costs,” she said.
“With more than 5,600 Australians losing their life to a blood cancer each year and more than 186,000 people expected to die from blood cancers by 2035, ensuring increased and sustained investment in research is more important than ever to drive down these figures and save lives.
“Over the past two decades, the Leukaemia Foundation has proudly invested more than $54.5 million into research, including supporting over 370 researchers across 290 research projects, through PhD scholarships and research grants, at over 50 hospitals, research institutes and universities.
“On behalf of the Leukaemia Foundation, I sincerely congratulate Basit Salik, Dr Jamie Kuzich and Dr Julian Grabek and we look forward to seeing their research translate into improved results for people in our community living with AML and MPN.
“The more we all know about blood cancer and best treatment options, the better our chances of curing and conquering this complex set of diseases, and the closer we are to realising our united vision to see zero lives lost to blood cancer by 2035.”
The Leukaemia Foundation has been supporting Australian blood cancer research and the careers of promising scientists and clinicians for over 20 years. These PhD Scholarships, valued at $130,000 each, are part of the Leukaemia Foundation’s National Research Program which has invested more than $54.5 million into research since 2000.
The Leukaemia Foundation is proud to partner with HSANZ – an organisation which promotes excellence, advocates for improvements in the care of patients with blood cancer and supports blood cancer research. Together the Leukaemia Foundation and HSANZ aim to help more medical and science graduates pursue a research career in blood cancer through co-funded PhD scholarships.
The Leukaemia Foundation thanks Brydens Lawyers and the Bourne Foundation for their generous contribution and support to the PhD Scholarship program.
The Leukaemia Foundation is committed to funding research the drives rapid advancements in treatments, diagnostics and novel therapies and gives Australians access to the latest treatments through clinical trials. More on the Leukaemia Foundation’s National Research Programhere.
The Leukaemia Foundation receives no ongoing government funding, and the National Research Program relies on the continued support of generous donation. To find out how to support the Leukaemia Foundation’s National Research Program call 1800 620 420.
“Donations allow us to continue to invest in Australian blood cancer research and to support the next generation of researchers, driving this type of innovative research for better treatments, better care and ultimately a cure for blood cancer,” Ms Struthers said.
Learn more about the successful research projects here.
Find out more about AML here, more about MPN here, or subscribe to the Leukaemia Foundation’s disease-specific newsletters here.
About The Leukaemia Foundation:
The Leukaemia Foundation stands with Australia to help cure and conquer blood cancer – with care. Together we are attacking every blood cancer, from every direction, in every way we can. We stand beside every Australian to be their voice and their someone-to-turn-to, fighting to get them access to the best care. We also accelerate research that’s delivering rapid advancements in blood cancer diagnosis and treatments. Plus, we provide services and support that empower people living with any blood cancer to live well after diagnosis. You can learn more about the Leukaemia Foundation and blood cancer at leukaemia.org.au.
The Haematology Society of Australia and New Zealand aims to promote, foster and develop the discipline of haematology in all its aspects and particularly provides support and advocacy for research in haematology. More about HSANZ here.
Subscribe to Leukaemia Foundation news and updates
The Leukaemia Foundation has been supporting Australian blood cancer research and the careers of promising scientists and clinicians for over 20 years. These PhD Scholarships, valued at $130,000 each, are part of the Leukaemia Foundation’s National Research Program which has invested more than $54.5 million into research since 2000. To date that funding has supported over 370 researchers across 290 research projects, through PhD scholarships and research grants, at over 50 hospitals, research institutes and universities.
Accelerating research and providing access to best practice treatments are two key research priorities of the Leukaemia Foundation and were identified as key priority areas in the State of the Nation: Blood Cancer in Australia report and recently released National Strategic Action Plan for Blood Cancer. These reports show us while significant gains have been made, it is projected that more than 186,000 Australians may die from blood cancers by 2035. These reports highlight that research has the potential to reduce blood cancers mortality rates and the associated economic costs but to do so will required increased and sustained investment in research. That is why the Leukaemia Foundation is committed to funding research the drives rapid advancements in treatments, diagnostics and novel therapies and gives Australians access to the latest treatments through clinical trials.
The Leukaemia Foundation thanks Brydens Lawyers and the Bourne Foundation for their generous contribution and support to the PhD Scholarship program.
Myeloproliferative neoplasms (MPN) are clonal haematological disorders of stem cells. These stem cells undergo a mutation that drives an overproduction of blood cells. Throughout the course of the disease the stem cells are driven by specific mutations (JAK2, CALR and MPL) but over time additional genetic mutations are acquired leading to progression of the disease to either secondary myelofibrosis and bone marrow failure or acute myeloid leukaemia. These outcomes have limited treatment options and have a poor prognosis.
High risk stem cells with the potential to develop into leukaemia can be identified early in the disease but are often a “needle in a haystack” when compared to the rest of the MPN stem cells. By using cutting edge single cell technology, the aim of Dr Grabek’s project is to separate each individual cell of the MPN stem cells. Through a combination of mutational analysis by novel nanopore technology and assessment of downstream gene signalling they will be able to determine the early stages of leukaemia development in these disorders. In future, it is hoped to establish which treatments have the potential to arrest these early changes and prevent transformation to leukaemia.
Over the last 4 decades, chemotherapy-directed management of acute myeloid leukaemia (AML) patients has remained largely unchanged. While most patients achieve complete remission after chemotherapy, most patients with AML relapse and ultimately die of the disease.
A high relapse rate in AML suggests that current standard therapies do not target these highly self-renewing leukaemia cells and that immune subversion by the primary tumour leads to an ineffective anti-tumour response. Cancer cells including leukaemias can adapt to oncogenic and/or environmental stressors such as chemotherapy, hypoxia, and metabolic stress. Indeed, several stress-induced molecules augment pro-survival signalling and aggressiveness in cancer cells. By contrast, either by direct recognition of stress-induced molecules on cancer cells or by exposure to environmental stress factors, immune cells also undergo functional impairment.
Basit and his team will investigate biological pathways that regulate cancer cell-intrinsic adaptation/aggressiveness as well as immune dysfunction by utilising patient samples and mouse models of AML. The team is hopeful that this research will lead to improved therapeutics that can effectively inhibit leukaemia growth with the potential of harnessing anti-leukaemia immune responses for durable disease control.
The Leukaemia Foundation receives no ongoing government funding, and the National Research Program relies on the continued support of generous donations. Donations allow us to continue to invest in Australian blood cancer research and to support the next generation of researchers, driving this type of innovative research for better treatments, better care and ultimately a cure for blood cancer. To find out how to support the Leukaemia Foundation’s National Research Program call 1800 620 420.
Chronic blood cancer diagnosis sparks Mel’s passion for awareness
Since receiving a shock chronic myeloid leukaemia (CML) diagnosis in July 2020, Mel Harris has learnt quickly that the so-called ‘invisible cancer’ can have everyday impacts beyond what many would expect.
Mel had been feeling unwell for months in the lead up to her diagnosis, always cold to the bone, constantly tired, experiencing night sweats and “horrific” back pain.
“I just explained everything away – thinking it was menopause, maybe depression or just the huge year we were having with the global pandemic,” explained the 47-year-old from Canberra.
“The first week of July, things got worse and I couldn’t physically get out of bed. My 18-year-old daughter, Mackenzie said to me, ‘Mum, I’m really worried’.
“That was enough to kick me into gear and I went to the gym the next day. Not long after I started exercising, I passed out and was taken to hospital!”
“I spent the next couple hours Googling the disease, reading about poor prognoses and aggressive treatment regimens – that was really scary,” said Mel.
“I then got transferred to a different hospital in Canberra to have a bone marrow biopsy and the morning after, the haematologist was able to confirm that it was actually chronic myeloid leakaemia (CML).
“Within about 18 hours, I’d gone from feeling like I could smash out a gym session to being diagnosed with a blood cancer.”
Mel was relieved when the haematologist explained that CML was an entirely manageable blood cancer which most people live with for the rest of their life and rarely die from.
“I was just thanking god, because Mackenzie wasn’t quite 18 at the time, it’s just the two of us and she was in the midst of finishing grade 12,” said Mel.
“My haematologist has been really good, explaining the full history of CML drugs. He’s been around for a while and told me how he could remember when this ‘miracle drug’ called imatinib was in clinical trials.”
Since starting on imatinib, Mel has experienced minor side effects of night-time nausea, bone pain, fluid retention under her eyes, a swollen spleen and neck.
“But my GP and haematologist work well together to address those issues as soon as they come up,” she said.
“It’s not hard to manage and I actually feel really lucky because some of the side effects I’ve read on the online support groups sound horrific.
“I do find the groups good for connecting with others and information sharing. I ran out of my drug one day and I remembered that someone had posted about a great chemist in Canberra who would have stock – that was really helpful.”
A couple of months into treatment, Mel started to feel like herself again and went into her haematologist’s office thinking she would be told she had beaten the leukaemia.
“I had taken my tablet religiously every night at the same time, I’d been exercising again, not drinking alcohol and maintaining a really healthy diet,” said Mel.
“I was having regular blood tests, my white blood counts and haemoglobin were looking really good.
“It had completely eluded me that I would still need leukaemia tests every three months and I would need zero detection of leukaemia to be cleared.
“He said to me, ‘You must remember at the end of the day, you still have blood cancer. Just give yourself a break’.”
Mel works as a capability and change strategist at the Australian Trade and Investment Commission (Austrade) in Canberra.
Oren fast-tracked to CAR T-cell therapy for rare Ph-like ALL
Diagnosed with a rare ALL sub-type last year, Oren London had only just begun chemotherapy before being accepted for CAR T-cell therapy in Australia.
A sports-loving 12-year-old, Oren had competed in a state swimming championship and weekend rugby matches in July 2019 when his mum, Fiona Snell noticed a series of changes in her son.
“Suddenly, he became really lethargic and lost motivation… he’d fall asleep anywhere,” explained Fiona.
“Then there was the bruising and weight loss, which I originally put down to puberty.
“After a sports injury in a footy game, he started having severe shoulder pain and he’d come out of physio sessions screaming.
“Then his appetite was almost non-existent, he began complaining of tummy aches, and was looking grey.”
After three weeks of these symptoms, with no improvement, Fiona took Oren to their local doctor in hometown Pottsville on the New South Wales north coast.
They were sent straight to hospital after the doctor noticed Oren’s spleen and liver were enlarged.
“We arrived at Emergency and got the red-carpet treatment straight through,” said Fiona.
Finally, after three hours of tests, the medical team told them that Oren had leukaemia.
“That’s when my whole world fell apart.”
Only a few hours earlier, Fiona had thought Oren would be given antibiotics and they’d be on their way.
“It was tough, especially having to break that news over the phone to my hubby, Jason,” said Fiona.
“I told him to get a bag ready and bring it up to the hospital with our daughters, Nylah, 9 and Amara, 10.”
Treatment resistance and organ failure
Oren and Fiona were medically transferred from the Tweed hospital to Brisbane, so Oren could begin chemotherapy immediately, and his diagnosis was confirmed as acute lymphoblastic leukaemia (ALL).
Four days into treatment, Oren’s kidneys started to fail, and he went to intensive care.
“The chemo started to attack all his organs and he developed tumour lysis syndrome*,” said Fiona.
Oren was put on dialysis to improve his kidney function and it took two weeks for his blood levels to improve enough to continue having chemotherapy.
“He ended up with high blood pressure, had seizures, and was sent back to the paediatric intensive care unit.”
CT scans and an MRI showed he had Posterior Reversible Encephalopathy Syndrome**.
Oren’s medical team became increasingly concerned that he had not achieved remission from his first month of treatment and ordered regular bone marrow aspirates and lumbar punctures.
Further studies of his bone marrow revealed that Oren had a mutation and sub-type of ALL, called Philadelphia-like ALL diagnosis (Ph-like ALL).
“We were told this particular mutation is quite strong and rare,” said Fiona, and this explained his resistance to chemo.
Preparations began for Oren to have a bone marrow transplant and he was set up to have full body radiation.
“His sister, Amara, was an exact donor match,” said Fiona.
Then, suddenly, Oren became a successful candidate for CAR T-cell therapy.
Fast-tracked to CART-cell therapy
Fiona said that Oren’s case, being so rare, was put before the board of CAR T-cell experts at the Royal Melbourne Hospital for consideration for the therapy, Kymriah® (tisagenlecleucel), which had only recently become available in Australia
“I had learned a little bit about CAR T-cell therapy through my research of Ph-like ALL,” she said.
“I understood it was normally for kids that had gone through two and a half years of treatment, had already tried a bone marrow transplant, and had a second or third relapse.
“They had to know Oren wasn’t going to survive the two and a half years of preliminary treatment for him to be approved for CAR T-cells after only three months of treatment.”
The London family was notified in November 2019 that Oren had been approved for the new form of immunotherapy and they travelled to Melbourne to have his T-cells collected.
“Oren was the first child from Queensland Children’s Hospital and the sixth child in Australia to have CAR T-cell treatment,” said Fiona.
“The Australian government had just given the funding and we were so lucky to have a supportive oncologist who really went to bat for us.
“His T-cells were sent to the U.S., to have the CAR-receptor put on them, which took about four weeks.”
During that time, the Londons returned to Brisbane and Oren had maintenance chemo before going back to Melbourne in January 2020 so Oren could receive his now ‘super-charged’ T-cells.
“We stayed for seven weeks and I don’t want to say it was a walk in the park but compared with what he had been through with the chemo, it was amazing,” said Fiona.
“He had a small reaction of high temperatures but when they did the bone marrow aspirate and a lumbar puncture 30 days later; we had hit remission.
“I got my boy back. I now have my smiling, eating, walking, talking 13-year-old back.”
Home to a pandemic
On February 23, the family returned to Pottsville.
“The girls had just returned to school full-time, and Oren part-time, when the COVID-19 pandemic hit,” said Fiona.
“I took the kids out a week before the schools made that decision to close. We had been through too much for too long to take any chances.
“It was a great time for us to bond again in our own home for the first time in six months. It really brought us back together as a family.
“Now the kids are back at school and Oren has started footy training and taking his position on the field for a full game.”
Looking to the future
For six months after his CAR-T treatment, Oren had monthly check-ups and bone marrow aspirates in Brisbane, and for the rest of his life Oren will need regular intravenous immunoglobulin therapy (IVIg) due to his non-existent immune system.
“We had hoped to switch to subcutaneous immunoglobulin which he could have injected weekly,” said Fiona, but unfortunately this was not possible, due to the current COVID-19 border crossing issues.
“At the one-year mark, in January 2021, we are due to return to Melbourne for his annual check-up.”
Improving access to CAR T-cell therapy
After their experience, Fiona is keen to see CAR T-cell therapy become a frontline treatment for others diagnosed with childhood ALL.
“If this is how they can treat kids with ALL down the track, and not have to go through any of that chemo for two and a half years, it will change the game completely,” said Fiona.
“We were very lucky because a year ago we would have had to fund a trip to the U.S. to even get on the treatment and I’ve heard of people selling their houses to do so.
“To my knowledge, it can be up to $500,000 to access CAR T-cell therapy there and the ongoing costs for IVIg are expensive.
“Research is progressing at such an impressive rate and I’m so thankful for all those people in the past that have been through the trials and testing to get CAR T-cell treatment to the place it is now.”