Same cancer, same drug but our access to treatment was anything but consistent
They’re three women all battling an incurable type of blood cancer, but Neda, Nikki and Shirley have felt hardship in very different ways.
Before lenalidomide was listed on the PBS, the breakthrough medicine could cost more than $194,000 for single course of treatment.
But it was an option that could help these three Australians to prolong their disease in remission.
Unable to pay the $1,000 monthly cost, Neda Masters (pictured above) from Queensland was on the verge of moving to America where she could get affordable access the drug.
The 46-year-old mum said: “We didn’t have a choice. Thankfully, my husband had a job lined up but I didn’t know what I was going to do if my family couldn’t live and work in America with me.“
Getting access to the best treatment was going to come at huge cost. We were unable to make the move to America because of the COVID-19 pandemic.
“Thankfully, the PBS listing in March means I can access the drug here at an affordable price.”
Nikki Wagner from New South Wales could only initially afford three boxes of lenalidomide, calling them her “princess pills” with each small tablet costing around $250.
Thankfully, her brother intervened and raised the $18,000 needed to start maintenance on this drug.
The 56-year-old said: “It cost about $5,000 for each box of 21 tablets. There was no way we could continue to afford them.
“However, following the initial costs outlayed, I was told I would be getting the drug on compassionate grounds through the drug company. From then on, I was able to get a box for less than $8, a life-changing discount.”
Shirley Irwin was not so lucky. The 71-year-old from Victoria used $54,000 from savings to pay for her lenalidomide which she took for eight months.
The mother-of-two said: “I’ve had some difficulty coming to terms with spending the kid’s inheritance on this medication. But they assured me, ‘we don’t want the money, we want you’.”
I needed better information about clinical trial options
Matthew Fogarty has spent almost five years regularly travelling to the other side of the world to collect the handful of pills that keep his blood cancer at bay.
After running out of proven, effective treatment options in Australia for his rare type of leukaemia, the 56-year-old stumbled across a clinical trial in America recruiting people to test a drug called ibrutinib, which wasn’t available in Australia at the time.
The father-of-three applied for entry to the trial and was accepted.
Nearly half a decade later, he has spent more than $100,000 of his own money travelling from his home in Perth to Washington DC every 12 weeks to pick up his next dose of the life-saving medicine.
“It’s been a miracle drug for me and may well have saved my life,” he said.
“I believe I’m the only person in the world with this type of blood cancer who has achieved complete remission on ibrutinib.”
“I hope other people like me have an opportunity to try this drug as soon as possible.”
Matt says he had access to the treatment options of his choice after he was diagnosed in 2004, but each time was unable to achieve full remission.
He felt his only option left was to try ibrutinib via Australia’s compassionate access program.
However, his application was declined because “there wasn’t enough evidence to prove ibrutinib could successfully treat this type of blood cancer”.
He added: “I’m disappointed no one thought to tell me about the clinical trial in the US, or even suggest I look.
I discovered it myself on Google and contacted the trial doctors myself.
Surely, I could have been given better information about clinical trial options at that time.
“The financial and psychological impact of the relentless international travel has been substantial, and I’m very fortunate to have had the support I needed from my family to get me through it. I realise not everyone is as lucky as I am.
“If there were more clinical trials here in Australia, it would open up access for many more people and potentially make a huge difference to their quality of life.”
I took control after becoming adrift in the system
The long wait for a diagnosis took its toll on Bronwyn Bisley, but her biggest challenges lay ahead as the information she desperately needed dried up.
After feeling run-down and noticing swelling in her neck, the mother-of-three visited her doctor where a CT scan seemed to show Bronwyn had breast cancer.
It was an opinion that set in motion a significant series of events: a referral to an oncologist, more appointments and scans, biopsies and, eventually, surgery.
But breast cancer was eventually ruled out and Bronwyn was instead referred to a haematologist 200km away in Melbourne.
Bronwyn said: “Finally, about three months after my first CT scan scare, my blood cancer diagnosis arrived – by Skype.
The haematologist said I would need chemotherapy, six months leave from work and she asked if I had questions. I had absolutely no idea what to ask.
“Then I didn’t see her again for a really long time.”
Bronwyn was unsure about what lay ahead. She faced “distressing” chemotherapy sessions and debilitating side effects, felt like she didn’t have enough information or support, and had to wait two months between seeing her haematologist.
Overwhelmed, Bronwyn took the frightening decision to press pause on her life-saving treatment.
“I didn’t want to be on that factory line for months, having no discussions with my haematologist, being so sick and only feeling worse.”
Bronwyn decided to take control. She dedicated time to get the information she needed. She spoke to experts and friends and eventually travelled to Melbourne, two hours from her hometown, to meet another haematologist.
Feeling empowered and supported, it wasn’t long before Bronwyn was back having more individualised treatment in a way that better managed her side effects.
The information she gathered also saw her make positive changes to her lifestyle that helped her recovery.
The 50-year-old from regional Victoria, now back at work, said: “I never experienced those horrendous symptoms or side effects again. I was more informed, and everything became a lot better.
“It would make a huge difference if everyone with blood cancer was given the information, ideas, connections and support they needed right from the get-go.”
Personalised cellular therapy gives Hunter a future
A cutting-edge cellular therapy, made possible by breakthrough research, has given seven-year-old Hunter hope for a brighter future.
Hunter was three years old when he was diagnosed with an aggressive blood cancer, and standard chemotherapy and transplant treatments proved unsuccessful.
“We found out Hunter has a very rare chromosomal abnormality in his leukaemic cells,” explained Hunter’s mum, Kate.
“Because of that, I always knew he was going to relapse. I didn’t think it would be as early as he did, but in my hearts of hearts, I knew.”
Blood Cancer Taskforce member Dr Rishi Kotecha is Hunter’s oncologist at Perth’s Children Hospital and advocated for Hunter to receive newly approved CAR T-cell therapy at the Royal Children’s Hospital in Melbourne.
Hunter was just the tenth child in Australia to undergo federally funded, CAR T-cell therapy, only qualifying for the treatment after leukaemia cells were found in both his central nervous system and bone marrow.
“This is unlike any treatment he’s ever had before,” said Kate. “His T-cells were extracted and sent to America to be re-engineered.
We then got them back, and he was given a small 10ml syringe of these new ‘super cells’.
Even though the process of engineering the cells and having them returned is complicated, from Kate’s perspective, it was quite straightforward.
“It was relatively simple, almost too simple, but it put him into remission.”
Hunter’s dad, Dave, is adamant research is the key to making a difference for families struggling with blood cancer.
“It’s because of research Hunter has been given another chance,” Dave said.
“It means everything to people like us who have seen our son struggle through these toxic treatments for over half his life.”
“The more support we can offer to research and clinical trials, the better.”
“It’s sad Hunter had to go through the trauma of his transplant, because he only started feeling like himself again nine months after the transplant,” added Kate.
“It only took six weeks after CAR T-cell treatment to get my happy, vibrant, healthy, energetic, little boy back.”
Drug discovery has remarkable potential for high-risk childhood leukaemia
Exciting research is laying the groundwork to develop a promising new targeted therapy for aggressive subtypes of childhood leukaemia including infant acute lymphoblastic leukaemia (ALL).
Lead investigator, Dr Michelle Henderson is a senior scientist, project leader and joint Research Manager of Molecular Diagnostics at Sydney’s Children’s Cancer Institute.
Before moving to the Children’s Cancer Institute, Dr Henderson spent 10 years working on the genetics and molecular biology of breast cancers at the Garvan Institute of Medical Research.
“Fourteen years ago, the opportunity to move to the Children’s Cancer Institute came up,” explained Dr Henderson.
“After spending years studying individual genes involved in cancer, I wanted to take a step closer to the clinic where I could potentially discover new treatments and have a more direct impact on people with cancer.”
While major research advancements have significantly improved survival rates in childhood leukaemia, Dr Henderson and her team are working to target certain subtypes of childhood leukaemia that still have very poor prognoses.
These include children who fail induction treatment, relapse during treatment or whose leukaemia harbours chromosomal rearrangement of the Mixed Lineage Leukaemia (MLL) gene*, an abnormality that occurs in 90% of infant ALL, with a survival rate of less than 50%.
“It can be an extra challenge with children as their bodies are still developing and these chemotherapeutic agents that work so well for leukaemia can still be very harmful to the patient,” said Dr Henderson.
“If it’s a more aggressive cancer then that child will receive more aggressive treatment and that can affect them later in life, leading to physical problems such as heart disease, osteoporosis, infertility, obesity, or even the risk of a second cancer.
“This presents an urgent need for the development of novel treatment strategies incorporating more selective, targeted therapies, allowing for a reduction in chemotherapy dosage and toxicity.”
For the past 10 years, Dr Henderson’s lab has collaborated with a lab in Buffalo, New York, conducting ‘screens’ with the aim of finding new drugs which specifically kill cancer cells without affecting normal cells.
Together they have discovered a new drug, OT-82, which has ‘remarkable’ potential to improve treatment in aggressive childhood leukaemia.
This grant was co-funded by the Leukaemia Foundation, The Kid’s Cancer Project and Cancer Australia.
“This drug, OT-82, blocks the production of a cellular biochemical called nicotinamide adenine dinucleotide (NAD) which rapidly dividing cancer cells can be dependent on for energy,” said Dr Henderson.
“NAD is also a co-factor for a number of enzymes that help the cell repair itself and so leukaemia cells can require a lot of it because they’re continually growing and need to repair themselves all the time.
“Based on the knowledge that cancer cells depend on NAD more than normal cells, researchers have tried for many years to design a compound that actively targets and inhibits production of NAD. But a suitable compound was yet to be found.”
Although not looking to target this pathway in particular, Dr Henderson and her collaborators in the U.S. came upon such a compound through a screening strategy aimed directly at blood cancer cells.
“We were surprised when the compound that came out of the search appeared to be an inhibitor of an enzyme called NAMPT (nicotinamide phosphoribosyltransferase), which is necessary for producing NAD in the cell but whose association with blood cancers was unknown,” she explained.
“This particular compound universally kills blood cancer cells, but the normal blood cells just go into a pause.
“The normal blood cells don’t die, they are just in pause and then when you stop treating them, they rejuvenate again, whereas the cancer cells don’t.
“It’s interesting that we’ve come across it through a completely blind approach of just screening thousands and thousands of compounds and found one that targets blood cancer cells.
“This compound seems to be very well tolerated so far in adult trials and is earmarked for going further into paediatric trials.”
With this grant, Dr Henderson and her team are laying the groundwork for these paediatric trials, by determining which children could be most responsive.
“Part of our research is to determine exactly which subtypes of leukemia will respond, both on a broad, phenotype level, and at a molecular level, to find which genes are expressed in that particular cancer,” said Dr Henderson.
“We want to have a set of biomarkers, or subtype markers, that say if a patient has this cancer and it expresses this gene or mutation, they are more likely to respond to OT-82.
“So far, we have found a set of very responsive patient samples that each have mutations in DNA repair genes.
“We think that when they have a weakness in their DNA repair, with the cancer cell having to grow so rapidly and requiring NAD for repair, that’s when they are particularly responsive to OT-82.
“We are also looking at how OT-82 can be used in combination therapy to promote the response to other drugs currently being used for leukaemia treatment.”
The impact of this project is further enhanced by a collaborative grant recently awarded to the Children’s Cancer Institute to deliver personalised medicine to every child in Australia.
“It’s going to become a reality that across the country every child’s cancer will be sequenced,” said Dr Henderson.
“Such a completely individualised approach to treatment means that OT-82 could have an incredible impact on patient survival outcomes.”
Inhibiting NAD also appears to be relevant to some other cancers that depend on the same pathway.
“They might be solid tumours like sarcoma or brain tumours with certain genetic mutations you can screen for that cause dependence on this particular pathway,” said Dr Henderson.
The next big challenge for the research team will be gearing up for a paediatric leukaemia clinical trial.
“That’s why this funding from the Leukemia Foundation, The Kid’s Cancer Project and Cancer Australia is so important,” said Dr Henderson.
“Even though a relatively small number of children may have these high-risk leukaemia subtypes, it will have a significant impact on survival outcomes for this group and may be applied across other cancer types.
“The whole team is so thankful to have the opportunity to gather this supporting evidence and make a real case for OT-82 to be taken to clinical trial stage for these deadly childhood leukaemias.”
*Also referred to as Mixed Lineage Leukaemia Gene Rearrangement (MLL-r). This occurs when a piece of DNA is swapped with another chromosome which results in two different genes being abnormally joined together. The resulting protein can no longer control the development of the blood system and blood cells grow out of control, resulting in leukaemia.
The Leukaemia Foundation’s National Research program has supported the careers of the brightest researchers and clinicians, like Matthew Witkowski, for almost 20 years.
His research is a prime example of how critical research funding is to understand the biology and genetics of blood cancers and to developing new treatments.
Matt’s career trajectory was kick-started when he won the under 11s footy grand final for Diamond Creek in Victoria! He has since moved from sport to science and, after completing his Honours at the Walter and Eliza Hall Institute (WEHI) in Melbourne, was awarded a PhD scholarship from the Leukaemia Foundation.
Now he’s working as a postdoc scientist at the New York University School of Medicine in the U.S. and his sights are focused on improving the effectiveness of CAR T-cell therapy.
When ALL News spoke to Matt, he had just presented on The relapsed B-cell acute lymphoblastic leukaemia immune microenvironment and won the first prize post-doctoral Eugene Cronkite 2019 New Investigator Award at the International Society for Experimental Haematology conference in Australia.
He explained that back in 2011, when he applied for a PhD scholarship, “the Leukaemia Foundation was very competitive, but I was lucky enough to receive it”.
Matt’s PhD, from January 2012 to December 2014, was valued at $120,000.
“It was my first scholarship. It was a big deal for me, and relieved a lot of the stress,” said Matt.
“You knew someone cared about what you were doing as a student and that it was worth investing in. That’s critical at the point when you are learning the lay of the land in science.”
“The Leukaemia Foundation was a big supporter of our lab and was a constant support and funding stream. Our lab thrived on that bit of stability,” said Matt.
“You do a lot of work all the time, in science. You’re constantly working, so you don’t want to worry about funding, especially when the Australian government can swing around in terms of how much they are investing in science.
“We were a small lab with one post doc, two students, and Ross as well. It was one of the few acute lymphoblastic leukaemia labs at WEHI at that time,” explained Matt.
“We were working on ALL because it is the most common cancer in kids and the most common cause of cancer-related death in children. I work on B-cell leukaemia, which is the most prevalent form of ALL.
“Students are the powerhouse of a lot of labs, especially ours.
“The other student in the lab, Grace Liu [also a Leukaemia Foundation three-year PhD scholarship recipient (2010-2012)] and I were producing a lot of the data.
“We both got meaningful papers out of it, which put us in good stead for building a career in the field” said Matt, and this was important for his career going forward.
Matt was investigating genes defective in leukaemia patients who showed resistance to chemotherapy, which would suggest that these particular genes dictated a patient’s ability to respond to chemotherapy.
“My work has focused on the Ikaros gene and defining how Ikaros interacts with other genes in a leukaemia cell to drive chemotherapy resistance and cancer development,” he said.
“By understanding these interactions, explanations for why patients who lack the Ikaros gene do not respond to therapy may become clear.
“Ultimately, this may lead to alternative therapy for ALL patients who would otherwise not respond to common chemotherapeutics.”
Matt had papers published in both Leukemia and The Journal of Experimental Medicine, and prior to completing his PhD, he went to a conference in Colorado in the U.S. where he met his current boss, Iannis Aifantis, an internationally recognised immunologist and cancer biologist, who heads a laboratory at New York University (NYU).
“He had read our papers and said, ‘do you want to come to New York for an interview in the lab?’.
“To be honest, New York wasn’t on my list. It seemed a little daunting. However, Luisa Cimmino, a previous postdoc with Ross Dickins, who was in the Aifantis lab, said ‘come to New York, it is really nice here’.
And so Matt went to further his career and research in New York. He went from a lab of four people to being a postdoc in a lab of 29! He’s still there now, continuing his work in ALL, “and it has been great ever since, just working away”, he says.
“I was able to extend on what I did in Ross’ lab. I worked in the same disease, ALL, but new technologies were coming out from the States and I could use them straight away.
“Leukaemia is a very complicated disease. You have a cell that is abnormal and it grows and grows in your bone marrow and spreads.
“What we did in Ross’ lab during my PhD, was provide really valuable information about what the genetic changes were in cells that made them transform into leukaemia. We used very novel tools to do that.
“Ross had brought that back from America and we took advantage of that to understand what underpinned leukaemia emerging and causing disease, and treatment resistance.
“When I went to America, I thought; how does the bone marrow itself influence the leukaemia? It obviously doesn’t grow on its own. It grows by interacting with everything around it.
‘When a patient presents with the disease that is throughout their bone marrow, then they get treatment, a small amount of leukaemic cells will just hang around and eventually the patient may relapse with the disease.
“My question was, ‘is there something that actually drives that small population of cells that are resistant to therapy to hang around, and what is the influence of the environment on these cells that would mean they would eventually not respond to therapy and inevitably cause relapse in these patients’.
“I was able to do a lot of that in the U.S. where we had new technologies where we could look not only at the leukaemic cell, but also everything surrounding it.
“We could deconstruct and pull apart the whole landscape of the bone marrow and understand all of the components and how they were talking to the leukaemia to keep it alive.
“What we have been able to do at NYU is use novel technologies to understand the whole system and how it evolves over time. We think we might be able to intervene with how the environment keeps the leukaemia alive, as a means of improving therapy,” said Matt, first author on a paper about this work that was published in Cancer Cell in June 2020.
“If you just stop these populations of cells from supporting leukaemic cells, you might be able to improve therapies that are already quite good in leukaemia.
“By just taking into consideration that you don’t just treat the leukaemia, sometimes you have to treat the things around it that would potentially support it surviving. This is a new paradigm in a lot of therapies.”
Matt has continued to keep in touch with an Australian ALL patient, India Papas, who he met through the Leukaemia Foundation when she was young.
“Every so often I ask Jodie [her mum] how India is going, and she seems to be doing really well…she has grown up.”
Matt said, looking to the future, his holy grail was to understand why some patients fail CAR T-cell therapy.
“This therapy harnesses a patient’s own immune cells to kill their tumour. It was originally utilised at the Children’s Hospital of Philadelphia and St. Jude Children’s Research Hospital (Memphis) as a way to treat B-cell leukaemia.
“Initially, it looked great. It looked like taking T-cells out of a patient and repurposing their own cells to kill tumour cells was going to be a really nice curative treatment.
“But it turns out that now we are a few years out from those initial trials, they [CAR T-cells] are not as effective as we thought. There are patients relapsing.
“It is an expensive therapy as well. In the U.S., it costs USD500,000 for a single treatment with this drug.
“There have to be ways to mitigate the relapsing that emerges from this. Not all of them are because of the drugs or because the B-cells they are targeting are naturally resistant. Sometimes there are other mechanisms.
“My goal is to start a group that tries to understand why patients fail this therapy.
“My initial work, in understanding how the bone marrow is composed, provides a good platform to understand how the environment informs how these new immune therapies are working.
“That is the goal in my immediate future, to start my own group where I can do this… to be around these therapies and take advantage of the fact that patients get biopsies which lets us see how they perform over time and why they don’t respond or why they do.
“There is also something called Bi-specific T-cell engagers. They hook leukaemic cells up to cells in the body that, if activated, kill leukaemia cells.
“There is a drug, called blinatumomab, that has done pretty well in this kind of field, where you are depending on the environment to kill the cells by using CAR T-cells and blinatumomab.
“Once we understand what the environment is and how it influences the leukaemia cells, it might inform us which patients may not respond to these drugs. We have made the assumption that the environment is going to allow these drugs to work, but we don’t know that,” said Matt.
Matt said he was open to potentially moving back to Australia to start his own lab or to do that somewhere in America.
“I may come back to Australia but I’m not definitive about anything at the moment,” he said.
* Dr Ross Dickins subsequently moved to the Australian Centre for Blood Diseases at Monash University.
** Mark McKenzie was supported by a three-year Leukaemia Foundation Postdoctoral Fellowship (2010-2012).
Daratumumab – first new myeloma agent PBAC-recommended in years
For the first time in 13 years, a new agent with a different mode of action against myeloma, daratumumab (Darzalex®), has been recommended for Pharmaceutical Benefits Scheme (PBS) reimbursement.
At the July 2020 meeting of the Pharmaceutical Benefits Advisory Committee (PBAC), daratumumab received a positive recommendation for PBS listing as a second line treatment, in combination with bortezomib (Velcade®) and dexamethasone for patients with myeloma.
In a submission to the PBAC in June 2020, the Leukaemia Foundation provided consumer comments in relation to daratumumab, based on the everyday experiences of people living with myeloma.
Peter, a myeloma patient from Western Australia, said:
“This drug is proving revolutionary in the fight against this terminal blood cancer and should be available as a permanent line of therapy [as] it can extend or save lives.”
The Leukaemia Foundation’s submission also stated that, based on the summary clinical trial information provided, “we understand daratumumab-based combinations have demonstrated efficacy in comparison to other agents tested in head-to-head relapsed or refractory myeloma trials in terms of delaying disease progression and response rates, and have also been shown to lead to molecular remissions in a greater number of patients with relapsed multiple myeloma”.
The PBAC noted in its recommendation that daratumumab monotherapy would be provided by the sponsor (Janssen), on a compassionate basis, to all eligible relapsed and/or refractory (R/R) myeloma patients who have no other PBS-funded treatment options.
A study, published in an August 2020 online issue ofJournal of Hematology & Oncology, confirmed and extended the previously known effectiveness and tolerability of daratumumab plus standard of care (bortezomib/dexamethasone) as a treatment for R/R myeloma.
The Leukaemia Foundation also made a submission to the PBAC for carfilzomib (Kyprolis®).
“We received eight responses to the request for feedback on this submission,” said Emily Forrest, the Leukaemia Foundation’s Head of Policy and Advocacy.
“Views amongst patients and their families/carers were mixed, with some concerned about the side-effects of the treatment,” said Emily.
“There is a high unmet need for new treatments for myeloma, which is currently an incurable disease which becomes progressively harder to treat after each relapse as patients become refractory to different treatments.
“We believe that the listing amendment for carfilzomib would provide clinicians with additional choice in therapy regimens for patients with refractory myeloma.”
Carfilzomib also received a positive recommendation to amendments to the dosing regimen and a change to a streamlined authority level, as sought by the sponsor (Amgen Australia).
Emily said the Leukaemia Foundation would provide submissions to the PBAC for consideration at its November 2020 meeting for elotuzumab (Emplicit®) and ixazomib (Ninlaro®) for patients with R/R myeloma.
Read Shirley Irwin’s experience with myeloma and a range of treatments including carfilzomib and daratumumab. (add link to story)
Shirley’s “so well” on her latest treatment – daratumumab
Shirley Irwin has had radiotherapy and two transplants, she’s dipped into savings to access treatment, had surgery, five different lines of treatment, and relapsed twice.
Despite all that has happened since her diagnosis with high-risk myeloma in May 2018, Shirley says, “I would say I have had a milder journey”.
Now on the monoclonal antibody, daratumumab (Darzalex®), which she started in July 2020, Shirley doesn’t know what her next option will be, but she’s prepared to personally pay for access to new therapies again, if they are not available on the Pharmaceutical Benefits Scheme (PBS). She and her husband, Bruce*, have a second property that they are prepared to sell, if necessary.
Now though, Shirley says she’s “so well, feels so good and is absolutely normal except, except weak to walk”. The daratumumab is working for her, she has no side-effects and hopes to continue this treatment on an ongoing monthly basis.
“If I could coast along like this, it would be lovely,” said Shirley.
Myeloma diagnosis and initial treatment
Myeloma came out of nowhere for Shirley, appearing as a sudden pain “that was scary”, while on holiday. She and Bruce had been away for six weeks in their caravan, had met up with friends from Perth, and were at Hall’s Gap.
They continued down the coast and up to Canberra before Shirley decided the pain was too great to go any further.
“It was leaving me uncomfortable and affecting my body. I said to Bruce, ‘I want to go home, straight home’,” said Shirley about returning to Ocean Grove, the seaside Victorian town where they have lived all their married life – 45 years.
She went to the doctor and after some tests a lesion was found on her spine and she was told she had high-risk myeloma. She was 69 and knew nothing about myeloma.
“I’d never had surgery, I’d never been ill; it was a big learning curve,” said Shirley, now 71.
Treatment began immediately. Radiotherapy on her spine, to shrink the lesion, before induction treatment with bortezomib (Velcade®) and a stem cell harvest, in preparation for an autologous stem cell transplant in October.
“I didn’t have any big hiccups, no big infections or anything like that. All was well,” she said, describing her 16 day-stint in hospital at Geelong for the transplant.
“Then I rallied around to have a luncheon for my 70th.”
That was in November, and her condition then was “only just strong enough” and she wasn’t eating much.
“I slept a lot,” she said. “I slept on the terrace in the sun, on the couch, in the caravan. I went from place to place until I got stronger. It was tiring, but it was fine. You just do what you have to do.”
Her second stem cell transplant
Shirley “took it as it came” until March (2019), when she had her second transplant. By then, her paraprotein level, which the first transplant had brought down to two, had risen to four.
“When I was first diagnosed, it was 75, which was ridiculous,” she said.
Due to her myeloma being Stage 3, she knew she was to have another ‘piggyback’ transplant.
“They had harvested enough stem cells to give me two transplants and it’s not uncommon to have two,” said Shirley.
“By the time I was due to have it, I’d forgotten the first one… but it didn’t take long to remember!
“I think I did the transplant very bravely and I rested for another couple of months after that.”
Shirley relapsed after two transplants
“Then in June, I relapsed,” said Shirley.
The myeloma had come out through the soft tissue in her left buttock.
“I thought… that’s a muscle or something… and took myself to the physiotherapist who manipulated it. Little did I realise that was the relapse.”
Shirley had expected to go through a course of treatments, starting with thalidomide, then lenalidomide, “then the next one, and the next one, and the next one… until where I am now”, she explained.
But her haematologist said, “thalidomide wouldn’t do anything, we’ll jump straight into lenalidomide with carfilzomib, but you can’t have both on the PBS”.
The decision to pay for therapy
Therefore, to have both treatments together, as a combination therapy, Shirley would have to pay for one of them.
“The lenalidomide was the cheaper of the two,” she said.
“My daughter, who was with me at the time, said, ‘well, if that’s the option, that’s what’ we’ll do’.”
But Shirley wasn’t comfortable with this decision initially.
“It meant spending our money for retirement. There wouldn’t be any cash left and there would be less when we’re gone.
“It caused me a lot of stress and took me a while to come to terms with spending the kids’ inheritance on this medication, but the family assured me, ‘we don’t want anything, … we want you’.”
Bruce had worked out that the cost of Shirley’s treatment to that point, accessed via the public medical system [the Irwins don’t have private health cover or receive a pension], was around $450,000. He convinced her and she subsequently agreed, that paying $60,000 so she could have two treatments at the same time, which her specialist said, “was the best recipe for her”, was a “pretty fair go”.
Shirley got access to the more expensive treatment, carfilzomib, through the PBS, and began the lenalidomide/carfilzomib regimen in June.
“I settled into that really well,” she said.
By October, Shirley had gathered strength. She and Bruce went on a “special family holiday” to Noosa in Queensland, along with her sister, Heather, and husband, John, daughter, Paige and her husband, Dan, and their three boys, and son, Saul.
Both Paige and Saul, live close-by to their parents.
“One’s just across the bridge at Barwon Heads and one’s round the corner,” said Shirley.
Another relapse and more treatment
For nine months, Shirley did “really well” on the combination therapy until the myeloma appeared again, in April 2020, this time in her thigh bone, causing a fracture.
“I’d relapsed again,” said Shirley.
She was told the myeloma had cloned and was no longer responding to the lenalidomide/carfilzomib. She needed a different treatment, but first she had to have more radiotherapy, and before she could have that, she needed surgery to put a pin in her right leg, from her hip to her knee, to secure the bone.
That happened within days, “which was super”, said Shirley as she couldn’t weight-bear and “it was so painful”.
“It took six weeks to get over the surgery, but then after a week or so I could have the radiotherapy. Now I’m fine in that leg.
The protocol to access daratumumab
“Then they had to start me on something else. Pomalidomide was next on the list, so I had that for a month. Even though they felt it wouldn’t do anything, you have to go through it to get the next, daratumumab.
“That’s the only time I felt anger, when the carfilzomib stopped working. It made me angry that I had to wait before I could go on the daratumumab,” said Shirley.
Scans showed spots on Shirley’s ribs and one at the top of her arm, so she had two rounds of chemotherapy to treat these, along with six cycles of daratumumab.
“I’m absolutely fine on the daratumumab,” said Shirley.
It’s a four-hour infusion every Thursday in the day ward, and she hasn’t had any of the side-effects she experienced on previous treatments – constipation, diarrhoea, tummy or bowel pain.
“On the first day my body races a bit and I get a bit tired but that’s all and of course, I’ve lost my hair again from the chemo.
“But I think I’m at the end of the line of what I can have,” said Shirley matter-of-factly about what treatment she may have next.
“I’m just going along. I feel well and I’m happy being at home with my husband.
“You know with COVID, you can’t do anything anyway, I still don’t feel I’m denied anything. This time that I have can’t be a high time because of COVID.
“I don’t walk so much anymore, well, not a long way, I haven’t got that strength, but we’ve got a light wheelchair, which I loathe, and I have been in it to go along the river.
“And we’re near the beach and it’s quite lovely and my husband likes to walk.”
Shirley loves to quilt and has sewn since her childhood. She and her sister, Heather, ran a dedicated quilt shop together for many years at Geelong, then Shirley worked at a haberdashery at Ocean Grove prior to retiring.
“I’ve got plenty here [at home] to sew. I love all my fabrics and there is so much that I want to do. I have a sewing workroom but find it very hard to go in there,” said Shirley.
After her myeloma diagnosis, Shirley couldn’t see the point, knowing the treatment “was just to keep you alive and as well as could be”.
“I did try to ignore the term, but it really has been palliative care,” she said.
“When I was diagnosed, the diagnosis was terminal. I know there’s no cure for myeloma, but I wasn’t expected to get 15 years out of it.”
After Shirley’s first relapse, she pushed for a prognosis and was told, “well, without treatment, maybe six months”.
“But it didn’t worry me, it was just a fact,” said Shirley, who is now heading towards three years down the track.
Dealing with a loss of choice in her life
“So that’s why if I went into my sewing room, it was sad,” she said, describing a sadness that was “different… not scary… not complaining… just not good”.
“I didn’t like that my choice had been taken away and it’s hard knowing that.
“At first, I thought, ‘oh, what’s the point of looking out the window? What’s the point of pulling out that weed? What’s the point of… ?
“But it’s okay. I go along with it now happily, and what will be, will be.”
“I’ve brought things out of the sewing room and have done a bit of handwork downstairs,” said Shirley.
And she’s teaching her three grandsons to sew.
“When they were little, they would sit on my knee while I sewed.
“I’ve got my eight-year-old [Finn] and six-year-old [Darcy] on the sewing machine. It’s just delightful, and they are so precise,” said Shirley about her daughter’s children.
“I put a box under the foot press for Darcy, so he can reach. His chin’s just above the machine.
“I show them where to sew and where to line it up, and they love it because they’ve got strips of fabric that become something.”
Their younger brother, Reuben, aged three, watches on.
They call her Grandma and sometimes, when Shirley is well enough, all three stay the night.
“It’s lovely. I follow them to their bedrooms and kiss them goodnight and the oldest one loves to cook. When he comes to stay, he cooks my egg and asks, “how would you like your egg this morning Grandma?”.
What will be, will be
“My thing has always been, what will be will be, so let go of the fear because someone is looking after you.
“The doctors are wonderful, the treatment you’re getting is great, and it changes if you change. You only have to let them know if you’ve got a side-effect and they can make an adjustment.
“I feel for my husband in the future, but he’s really strong and is busy doing things.
“We don’t worry about the ‘when’ or the ‘what after’.”
“We have a property down at Wye River. He was a builder and he’s nicely preoccupied with plans for that. If we do sell it, it needs to be renovated and extended, so that’s what he’s doing.”
Research aims to improve QOL by decreasing treatment toxicity
Research aims to improve QOL by decreasing treatment toxicity
Exciting research is examining whether a new inhibitor can be used to prepare myeloma patients for bortezomib and other myeloma therapies, to increase the efficacy and potentially decrease toxicity of these therapies.
Dr Vandyke was awarded a Priority-driven Collaborative Cancer Research Scheme grant in 2019 to build on her finding that the novel N-cadherin inhibitor, LCRF-0006, can dramatically increase the antitumour efficacy of low dose bortezomib (Velcade®) treatment. This grant was co-funded by the Leukaemia Foundation, Cure Cancer Australia, and Cancer Australia.
“The project has been a long time in the making,” said Dr Vandyke.
“We’ve been working on a N-cadherin inhibitor (LCRF-0006) as a potential target for myeloma for almost 10 years.
In this project, Dr Vandyke is looking at one particular drug (bortezomib) that’s used in the majority of myeloma patients and which causes peripheral neuropathy in about a third of these patients.
“This is a really horrible side-effect affecting the nerves in the extremities. It causes pain in the hands and feet, pins and needles, numbness, and burning sensations – it’s really nasty,” she said.
“Bortezomib, as well as targeting the myeloma tumour cells, also targets some of the long nerve fibres that go into the hands and feet. It targets the long axons of these nerve fibres and causes damage.”
Dr Vandyke’s project will look to increase the way the drug is delivered intravenously from the bloodstream to the cancer cells.
“The way bortezomib moves out of the blood and into the cancer cell is limited by the blood vessels as they’ve got a strong boundary around them that stops the blood from seeping out,” said Dr Vandyke.
“We think that this N-cadherin inhibitor is just opening up that barrier a little bit to allow the drug to get through more efficiently. It’s working more on blood vessels in cancer rather than normal blood vessels.
“You’re getting more of the drug into the cancer and can decrease the amount that’s going elsewhere in the body which should decrease those side-effects.”
The research team has just published a paper in the medical journal, FASEBBioAdvances, using a pre-clinical model showing that using LCRF-0006 effectively increases the effect of the bortezomib.
“This means we can actually use a lower dose of bortezomib and therefore we hope side-effects will stop because you’ll get a better anti-cancer effect with a lower-dose drug,” said Dr Vandyke.
The next steps will be to see if the side-effects are actually decreased and to optimise the drug to be ready for human clinical trials.
“Because this drug hasn’t been used in patients before, it would have to go through Phase I trials and safety studies before going on to larger clinical trials,” said Dr Vandyke.
“Also, because we don’t have a pharmaceutical company that’s making the drug, the next big hurdle would be funding – always a challenge.”
Dr Vandyke is motivated by the people who are living with myeloma and whose quality of life could be improved significantly by her work.
“As a scientist, you can get bogged down in the finer details of what you’re doing and you forget the big picture,” she said.
“We have a lot of engagement with patient groups that come for tours and education sessions at the lab.
“While advancements in myeloma therapies have improved survival rates significantly, toxic side-effects and treatment-related quality of life (QOL) have become increasingly important factors for patients.
“Many patients won’t want to take the drug if it’s going to have such a detrimental effect on their quality of life, regardless of the long-term survival outcome.”
Dr Vandyke is also passionate about fostering the next generation of researchers.
“I really enjoy the teaching and supervision side of things. I’ve got quite a few PhD students that I co-supervise with Prof. Zannettino and I’m mentoring a couple of junior researchers as well,” she said.
“One of them, Dr Krzysztof Mrozik, has been a real driver for this project – we couldn’t have done it without him.
“It’s also great for them to be able to talk to the patients and their carers and families and see this is why we’re doing what we’re doing.”
Dr Vandyke said she was, “incredibly grateful to Leukaemia Foundation supporters for enabling me, and my team, to do the work we do”.
“They have made this project possible.”
Dr Vandyke has used this funding support to expand her research group; to hire a technical support staff member, and support the research of a junior researcher.
“These grants are given to some of the very best emerging talent from around Australia, and I am proud to be included in this group.”
Navigating childhood blood cancer during a pandemic
This Childhood Cancer Awareness Month, we’re celebrating little legends like three-year-old, Archer Bermingham. Archer spent nine months, hundreds of kilometres from home and across state borders, undergoing life-saving blood cancer treatment during the COVID-19 pandemic.
Hailing from Lennox Head, a small coastal town in northern New South Wales, the Bermingham family live just a couple blocks from the beach and were enjoying the first weeks of summer, swimming and playing outdoors.
“Arch had started taking day naps for the first time in a long time and we thought it was because he was so active and wearing himself out,” his mum, Claire, explained.
“He had a couple of nights when he had fevers, so I had given him Panadol and he was able to go back to sleep.
“But after a couple of days we took him to our doctor who ordered urine tests which came back negative, but his night fevers were persisting.”
The morning of his diagnosis, Claire noticed he was limping and then a tiny speckled rash had started to appear on his abdomen.
“We returned to our doctor who sent us straight to the local emergency department for blood tests and possible imaging,” said Claire.
“It was there we were advised of suspected leukaemia and Archer was transported to Brisbane that evening where it was confirmed he had B-cell acute lymphoblastic leukaemia (ALL).”
The family travelled to Queensland Children’s Hospital in Brisbane, a 360km four-hour round trip from their home across the New South Wales-Queensland border.
“Archer underwent five phases of intensive chemotherapy, achieving remission in January 2020, which was a huge relief,” Claire said.
“Initially, we were told this intensive treatment would only last four to six months, but it’s ended up being almost nine.”
“There’s only so much tiny bodies can take, and we’ve had a few delays here and there when his body just needed a little bit of time to recover.”
The family of four, including Archer’s dad, Matt, and one-year-old baby sister, Lara, stayed at a Leukaemia Foundation Patient Accommodation Village for the duration of Archer’s treatment.
“From the day after Archer was diagnosed, we had a beautiful unit to call home and that’s just meant the world to us,” said Claire.
“It’s such a beautiful community feeling with the other families. The kids can play safely and we’ve made some beautiful friends.
“It’s so nice to know we’re not alone in this, especially during this pandemic. We just wouldn’t have felt comfortable having Arch in a public hotel.
“We felt so safe there knowing that everyone else is in the same boat and taking the same precautions. It really became our safe haven.”
Archer has now completed his intensive treatment with flying colours and will start the maintenance phase of treatment, which will take 18 months.
“We have had a few teething issues getting used to dosages and the terrifying free-fall of being let loose back into the real world,” said Claire.
The family were able to return home on 10 September 2020, just in time to celebrate Lara’s second birthday.
“It’s lovely to be back home, the COVID-19 border closure had been really difficult, and we hadn’t seen our families for over month,” said Claire.
“Arch will be able to have his six-weekly reviews, blood tests and port-flushes at Lismore Base Hospital and then we have special consideration to return for Brisbane for his three-monthly maintenance treatment.
“These will just be day trips where Archer and I will only be allowed to come straight to the hospital and remain completely isolated for his treatment.
“I’ve been told this process is very strict and can be intense, but at least we can still access the treatment he needs in Brisbane. Hopefully, everything stays on track and the travel restrictions will ease soon.”
Claire has also become passionate about raising awareness of childhood cancers and the long-term effects it can have.
“There is a lot to learn. When Arch was diagnosed, I didn’t even realise leukaemia was a form of cancer and just went in so blind,” Claire said.
“You’re in a situation where you’re making really critical decisions, on not a lot of sleep and with limited knowledge.
“It’s hard to blindly trust people with your child’s life but you really have no choice.”
She has since made it her mission to learn everything she can about Archer’s blood cancer and treatment.
“I felt the tiniest bit more steady by educating myself when our world was falling apart,” she said.
“But then the reality hit me like a tonne of bricks. Although the initial diagnosis is still the worst moment of my life, I was really at my lowest a couple of months after.
“I feel like if I’d been prepared from diagnosis with the knowledge of long-term implications, it wouldn’t have come as such a hard blow when that realisation did hit.
“It’s tough because the hype has worn off from the outside world, everyone goes back to their lives but yours is changed forever and you realise you’re in it for the long haul.”
Claire’s advice to other parents is to just take it ‘day by day, hour by hour, minute by minute and keep putting one foot in front of the other’.
“Your family is stronger than you believe. Your child is stronger than you’ll ever know. And you are stronger than you give yourself credit for.”
Claire’s top tips for parents:
Trust your instincts, be kind to yourself, cry in the car, eat the chocolate.
Always, always be nice to your nurse; they will save your child more times than you realise.
Talk to other parents; no two stories are the same but no one else will truly get it.