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Expert interview with Dr Cecily Forsyth on how to live your best life with MPN

Expert interview with Dr Cecily Forsyth on how to live your best life with MPN

Dr Cecily Forsyth and the nurse practitioner Jacqui Jagger
Dr Cecily Forsyth and the nurse practitioner Jacqui Jagger

Dr Cecily Forsyth talks to her MPN patients “a lot” about what they can do to improve their health, often highlighting the findings of a study on integrative medicine in MPN.

According to the results, published last year, of an international survey of 858 participants, integrative medicine offers unique symptom management strategies. These are based on interventions such as aerobic activity, strength training and massage for decreased MPN symptom burden, depression, fatigue, and higher overall quality of life.

“The SIMM study was coordinated by Ruben Mesa*, who is the king of MPN symptoms,” said Dr Forsyth, a clinical haematologist with a special interest in the MPNs.

“The survey showed that when you’re living with a chronic malignancy you can improve your symptoms by the things you do, not just the pharmacotherapy that your haematologist prescribes.

“Integrating physical activity, yoga, massage, art therapy–all kinds of different things–can improve your quality of life,” Dr Forsyth explained.

“This is an important message; it’s all about how to live your best life.”

Dr Cecily Forsyth in the Lofoten Islands, Norway
Dr Cecily Forsyth in the Lofoten Islands, Norway

Looking at the information and discussion in some posts on some Facebook support groups for MPN, Dr Forsyth felt there was too much negativity.

“Giving people a different, optimistic, message is really important,” she said.

“It’s about asking yourself, how do I live my best life, and how do I manage my symptoms so I can live my best life?”

“Helping patients with that is incredibly important, and it’s really well received; patients like to know that they can do things that can improve their symptoms.

“We know MPNs cause a lot of symptoms, but I don’t get bogged down about what’s causing them,” said Dr Forsyth.

“Whether your fatigue is from your MPN, stressful job, grouchy husband, or difficult children is irrelevant? What is relevant is that you are tired and how can we help you manage your fatigue to the best of our ability?

“It’s about moving your focus, because there’s no whizzbang therapy that means suddenly your symptoms have gone.

“It’s a way of managing them, and that will include patient-initiated activities and strategies,” said Dr Forsyth, whose nurse practitioner, Jacqui Jagger, also has an interest in symptom management in MPN.

“It’s about making sure you’re productive, you still have good relationships in your life, and you still have financial, work and vocational goals that all contribute to having a good quality of life. We try and work with our patients to achieve this.”

The SIMM study showed people do “a wide variety of activities” to try and help improve their lives, and those who exercise and who control their weight do have improvement in their symptoms.

“I explain to patients that they can try a wide range of activities such as yoga, strength training, Tai Chi, dance therapy …” and find what they enjoy and what inspires them.

“I tell patients repeatedly, exercise is needed. It’s absolutely fine to have a lovely massage but you also need to address the exercise and activity side of integrative medicine as well’.

“Participating in any kind of physical activity and strength training will improve your symptoms; you need to find an activity that suits you.

“I’m not a runner, I don’t enjoy that. But I’ve taken up pilates in the last five years, which I really enjoy.

“And I tell patients… that’s my time, when I’m not thinking about what work I haven’t completed? What am I going to cook for dinner? Have I done the washing? When am I going to do the letters?

Cecily Forsyth in Bolivia
Dr Cecioly Forsyth “planking” on the salt flats in Bolivia

“I’m too busy thinking, ‘how on earth am I going to get my leg up that high?”

“And I tell them that it clears the white noise out of my head. I can’t think about the stresses of work and life in a pilates class. I started pilates for my back but have found it to be just as good for my head as my back!

“I often give that example to patients and say, ‘you need to find what’s right for you’, whether it’s meditation or having a massage–things that allow you to destress.

“Doing an activity where you have to concentrate and focus on that activity, it could be art or ceramics, allows you to escape the worry about your MPN and life’s stresses.

“All this can help, particularly our patients with polycythaemia vera (PV) and essential thrombocythaemia (ET),” said Dr Forsyth.

“We want to try and make sure they’re in the healthy weight range, that they don’t smoke, and their cholesterol is under control… the whole range of interventions that will have an impact on symptom burden, quality of life, and risk of complications from the disease.”

Video consults and second opinions

Since the pandemic hit in 2020, Dr Forsyth has become an advocate of video call consultations and she’s convinced “they’re fabulous”.

“It’s one of the things that’s really improved the service for patients,” she said.

“I’m surprised by how useful they’ve been and, in the MPN patient population, it’s enabled people to see a haematologist with a little bit more of an interest in MPN, who are some distance away from where they live.

“They’re still under the care of their local haematologist, but they can have a second opinion or more direction if they’ve got tricky management problems with someone more experienced in MPN, without taking a day off work, without travelling, and certainly without crossing borders, which has been completely impossible.

“Some patients previously went to great lengths to travel to Gosford, where I am, and being able to offer telehealth is very time efficient for patients.

“I see a lot of patients with MPN, including second opinions, and have a little group of patients who’ve travelled to see me and whom I share care with their local haematologist,” explained Dr Forsyth. “I actually have a patient who has travelled from Far North Queensland for a second opinon.”

“He came down to Sydney for a reason, a couple of years ago, and saw me to ask me about interferon. It was in the early days of interferon being funded by the Pharmaceutical Benefits Scheme (PBS) for myeloproliferative neoplasms. His local haematologist hadn’t had much experience [with it].

“I still catch up with him once a year, which is much easier now there’s telehealth. I can have a good chat to him, and he’s shown me around his house and introduced me to his pets.

“It’s really a very enjoyable way of consulting,” said Dr Forsyth.

“I never have any hesitation, for my own patients, about organising a second opinion for them.

“And I always feel that if a patient wants a second opinion I try and ensure that it is opinion and advice that will benefit the patient and that maybe I would learn from also,” said Dr Forsyth, who is happy to make the referral.

“I tailor the recommendation to a person who is appropriate for the patient to see, and that’s not necessarily their next-door neighbour’s brother’s cousin’s uncle!

“If I organise the referral then patients can take all their results with them, a copy of all the pathology, all the imaging, and I can write a letter about why I’ve chosen what I recommended.

“I say to patients… if you do want to seek a second opinion, raise this with your treating haematologist. Talk to them about it and, if you feel comfortable, tell them why you would like a second opinion.

“Some haematologists don’t like it and feel upset about it. But we have to remember this is not about haematologists’ egos, it’s all about the patient and their disease, and whatever is best for the patient is fine by me.

“Sometimes people seek a lot of different opinions. There are patients that I have been the fourth haematologist they’re involved with, and I think that gets challenging for the patient.

Sometimes patients seek a second opinion because they haven’t got a good working relationship with their first haematologist, and you do need that.

“When you have a chronic illness, you need to be able to communicate effectively and feel that your haematologist cares for you and tries to assist you as best they can with your management.

“In the global era, sometimes people get advice over the internet in support groups that comes from outside Australia, where therapies are suggested that aren’t available or funded here.

“Patients need to bring these kinds of things up with their treating haematologist and say, I would like a second opinion. Sometimes they can phrase it as their family is keen for them to get a second opinion. It can be a bit easier to raise it from that perspective,” said Dr Forsyth.

Dr Cecily Forsyth kayaking in Norway
Dr Forsyth encourages her patients to consider a wide range of physical activities. Here she is kayaking in Norway.

How Dr Forsyth got into medicine, haematology and MPN

“I didn’t come from a medical background but was always interested in medicine and liked people, and being interested in science, the idea of going into medicine appealed.

“I enjoyed each term I did as a junior doctor, from intern to resident, and thought, ‘oh, I could be a gastroenterologist, or I could be… whatever.”

“Then, when I did haematology, I just loved it.

“I liked looking after people who were significantly unwell; that didn’t seem daunting. I didn’t mind talking to people about their life-threatening illnesses, and I liked the ability to do pathology at the same time; to see what their bone marrow looked like under the microscope, and care for the same patient,” said Dr Forsyth.

Today, due to her clinical load, Dr Forsyth is “just a clinical haematologist” but one who finds MPNs “an interesting group of illnesses”. This intensified “about two decades ago” when she took over the Australasian Leukaemia & Lymphoma Group’s PT-1 study as principal investigator from Professor Andrew Grigg.

“From there my passion for MPN has grown,” said Dr Forsyth and she calls herself “a community haematologist”.

She sees whatever type of haematology walks in the door of her practice on the Central Coast of NSW, 100km north of Sydney, but she has a love for MPN, which she describes as “a chronic blood cancer resulting in the overproduction of mature blood cells and associated with a wide range of significant symptoms that impact on quality of life”.

Access to MPN treatments

“We can do things better than we do for MPNs and that inspires me to raise patients’ awareness that there have been advances in diagnosis and management,” said Dr Forsyth.

“Overall, as a group, people with MPN are getting good care in terms of what is available for those patients.

“But sometimes you may have a haematologist who’s not experienced in using interferon [peginterferon alfa-2a (Pegasys®)].

“There has not been much pharma support available for haematologists and patients because of the very strange way it was PBS-funded, without a TGA indication,” Dr Forsyth explained.

“That’s why the MPN Alliance patient information sheets on interferon are so critically important in providing information for patients, and the clinicians about how to use interferon.”

The PBS-funding of Pegasys for patients with MPN, in 2018, “was really fantastic”, Dr Forsyth said.

“We’re still rejoicing in having pegylated interferon, as opposed to non-pegylated interferon. It’s been a good opportunity for patients.

“I think we will continue to see more and more data about the potential for interferon to modify the natural history of MPNs.

“Internationally, there is increasing evidence of the role of interferon and there’s an ultra-long-acting interferon which we don’t have in Australia, called ropeginterferon alfa-2b, that has less toxicity and equal efficacy [as Pegasys].”

Dr Cecily Forsyth hiking in Ethiopia
Dr Forsyth, hiking in Ethiopia with her husband, James Rogers, son, Harry Rogers, and daughter-in-law, Subeta Vimalarajah

Dr Forsyth said, disappointingly, ruxolitinib was not available through the PBS for Australian patients with PV who can’t tolerate or who have failed treatment with hydroxycarbamide (formerly known as hydroxyurea).

“They can’t get ruxolitinib until they’ve transformed to myelofibrosis (MF).”

Dr Forsyth said many centres are participating in clinical trials looking at adding other drugs to ruxolitinib for patients who are newly diagnosed.

“And for patients who have failed ruxolitinib, or are losing their response, studies are looking at what other drugs can be used to improve the response rate in that group.”

Dr Forsyth said the outcomes for young people–diagnosed under the age of 50 years–with ET was very good; they have a near normal life expectancy.

“Most people with ET and PV have a long survival, but on the other end of the spectrum–patients with MF–some of those with very high-risk disease have very short survival.

“Patients with high-risk myelofibrosis at diagnosis, are rapidly moved to bone marrow transplantation as their only curative option,” said Dr Forsyth.

And the group of patients with higher risk MF who are not eligible for transplant want to be participating in clinical trials, she said, “to try and improve their outcome because, unfortunately, MF can be a rapidly progressive and incurable malignancy”.

“There are more studies available with drugs that are more exciting than any other time before, and that’s really encouraging.”

“There’s very good data to show that patients who participate in a clinical trial do well and have better outcomes. That’s because they have access to treatments they wouldn’t have otherwise.

“Some patients may be motivated to participate in a trial because they are contributing to research that may help them and certainly may help other patients down the track,” said Dr Forsyth.

“I like to refer patients to the haematologist who is running a clinical trial, to make sure they have all the information they need and to minimise tests being repeated.

Information on clinical trials is available from ClinTrial Refer

Unmet needs in the MPNs

Dr Forsyth said all the MPNs can transform to secondary AML, many of them by transforming first to MF.

“This is a very unmet need, and AML that has arisen from MPN has a very poor outlook and, in that circumstance, can be very challenging.

“Often patients who you’ve known for a long time with their ET and PV, can suddenly develop changes that are consistent with transforming to AML. It can be very distressing for the clinician as well as for the patient,” she said.

“When transformation to AML occurs it is important to carefully consider what you can offer the patients, how successful treatment is likely to be, and their quality of life.

“For many elderly patients who transform to AML, we choose not to give them induction chemotherapy but offer them supportive and palliative care because, unfortunately, the outlook is grim.

“I think patients have to be realistic,” said Dr Forsyth. “Do you want to spend that time in hospital, having treatment that is unlikely to prolong your life, or do you want to be at home? Those kinds of discussions are difficult for everybody, most importantly, for the patient receiving that news.

“I try to reassure patients that the likelihood of transforming to AML is low.”

“I tell them there is a risk and that usually occurs when the disease has been present for a long time, but that risk is low, that risk is down the track, and let’s look at optimising what we can do.

“Unfortunately, there is no definite evidence that we can alter the natural history of the disease with currently available therapy.

“There is single centre evidence that interferon may have a role, so I might discuss that with patients when considering what cytoreductive therapy to recommend.

“Unfortunately, it does take patients time to cope following the diagnosis of an MPN especially when they realise that it is a blood cancer which is generally incurable.

“For many people, it will never progress, but it really is important in whatever circumstances to live your best life. I think that worrying about tomorrow today is very problematic and I try and move patients on from doing that too much.

“Worrying about what might happen tomorrow can really detract from how you live today.”

“A minority of people are so worried and consumed with anxiety about when their disease may or may not progress that they can’t enjoy actually being well today.

“We need to help those patients and I refer them to an oncology psychologist.”

Advice for the newly diagnosed

Getting advice and information from reputable sources is Dr Forsyth’s key tip.

“I always give my patients the MPN booklet from the Leukaemia Foundation and the card for the MPN Alliance Australia.

“I encourage them to live their best life, tell them there are things they can do to help with their life and that we can manage and control their disease to ensure their quality of life is as good as it can be. I tell them they can live a normal life, hopefully for a very long time, and in some cases with a normal lifespan.

“I try and give them a message of optimism, of self-control of symptoms, and motivate them about what they can do that helps with their quality of life.

“And I try and encourage them to get good support and use good sources of information from the internet and warn them that there are some less reputable sources of information on the web that should be avoided.”

*Professor Ruben Mesa is an international MPN expert who is committed to improving therapeutic options and quality of life for people with MPN, as well as being an active patient advocate.

ET or PV? That’s the question Sue’s been pondering for years

ET or PV? That’s the question Sue’s been pondering for years

Since her diagnosis with essential thrombocythaemia (ET) in 2013, Sue Taylor has been curious about whether she may in fact have a different type of MPN–polycythaemia vera (PV).

“It certainly was always at the back of my mind,” said Sue, 64, of Sydney.

Sue Taylor
Sue Taylor

Her search for the answer has seen her change her treating haematologist several times and go overseas to an MPN conference, so she could put the question to international experts.

Sue’s main interest in having an accurate diagnosis centred around her risk of thrombosis (blood clot) but was also about possible future access to new treatments and clinical trials

In 2009, soon after Sue took a voluntary redundancy from her sedentary but stressful job in the Australian Public Service, she got “some strange visual symptoms” which “was a bit concerning”.

When an ophthalmologist couldn’t find anything wrong, Sue put these episodes down to “just something happening” and got on with life, despite increasing episodes. (Later, Sue found out she had scintillating scotoma)

Sue and her husband, John, have spent much of their lives together working overseas and travelling extensively, especially after her retirement.

“We’ve packed a lot into our life, and it has been wonderful,” said Sue.

“We were in a fortunate position to be able to take a bit of time for us, while fit and healthy, to enjoy some time together doing things we wanted to do. For us that meant a lot of travelling.

“Having three close family members pass away in the recent past made us think you can’t take anything for granted.”

Four years on, when Sue went to her GP, a routine blood test showed her platelets were “fairly elevated” and, looking back at previous years’ blood results, it was apparent that although in the normal range, her platelet count had been increasing.

“At this point I was sent off to a haematologist and had the JAK2 test. It was positive and I was diagnosed with ET.”

“I felt very well and would never have thought I had anything wrong with me,” said Sue, then aged 53.

“Honestly, it’s a shock when you’re first diagnosed, but I was reasonably philosophical and just grateful it wasn’t something worse. I’d recently seen my dad go through motor neurone disease.”

Sue Taylor and grandson Teddy
Sue with her grandson Teddy when he was six months old

Her haematologist didn’t seem to think her visual symptoms were significant but put her on baby aspirin due to her high platelet count.

“The amazing thing, which I didn’t realise until a year later, was… I never had another of those episodes… except once, when I went off aspirin before having surgery.”

Being “an extremely curious person” and studying genetics for her science degree at uni, Sue had “done a bit of reading” on the internet about MPN before seeing her haematologist.

“I was told there was nothing to worry about but if my platelets continued above 600, then he might think about putting me onto hydroxyurea.

“When I asked about a bone marrow biopsy he said, ‘you don’t need to know about that yet’, which was like a red rag to a bull. He really wasn’t the right haematologist for me.

“I’m a very research and evidence-based sort of person, so I tried to see someone who was into research and preferably had an interest in MPN.

“I was fortunate to be linked up to a really special haematologist, who was involved in research, but MPN wasn’t his thing,” said Sue.

“Then I read about this third person who had an interest in PV and had been involved with PV study groups earlier in his career.

“I was referred to him, which was alright until he retired.

“He’d written a paper on platelet-mediated visual disturbances and was the first person who actually thought my visual disturbances might have some relationship to my ET. He was a bit excited because he thought I was a classic case.

“In the meantime, I did more reading and learnt a lot. I discovered MPNs are quite rare, there wasn’t a lot of research being done, certainly not in Sydney that I could find,” said Sue.

She came across an Italian research paper about JAK2 and PV.

“They worked out that a haematocrit–a measure of the volume of red cells in your blood–of 45 or below was the range for people with PV, to avoid a thrombosis which is the main immediate concern of haematologists treating MPNs.

“Although I’d been diagnosed with ET, I was very curious about this because my haematocrit was regularly measured at 47-48. I was concerned I was at risk of thrombosis, having a haematocrit that high.

“The JAK2 mutation was only discovered in 2005 and there were debates and different points of view about whether ET and PV were different diseases.

“There’s been research which shows a lot of people have been incorrectly diagnosed with ET who actually have PV,” explained Sue.

“I wondered if I had ‘masked PV’; a type of PV where you don’t quite fit the criteria to be diagnosed with PV, in terms of your blood counts, but it can be masked because of very low iron levels in your blood.

“I had very low iron levels, but I really couldn’t get any haematologist to be terribly interested in that. They were always interested in my platelets, but not my haematocrit.”

Sue Taylor with pegasys
Sue Taylor arriving home after picking up her first packet of Pegasys from the hospital August 2018. “It’s all packed up in ice!”

In 2017 Sue went to a patient conference, held by the MPN Education Foundation every two years in the U.S., that brings together eminent MPN researchers and clinicians from around the world.

“It was a fantastic experience. I met some of the MPN patient representatives in the U.S., and other patients.

“I still didn’t really get my question answered but I was told that, to be on the safe side, I should make sure my haematocrit was lower.”

Sue heard about pegylated interferon alfa-2a (Pegasys®) at the conference, and that in some cases it can lead to molecular remission.

“In Australia, haematologists were only talking about hydroxyurea, which I was concerned about taking because it exacerbated non-melanoma skin cancers, and I have very fair skin.

Sue had been on watch and wait and her only treatment was aspirin, until 2016, when she started having “funny spells”, didn’t feel very well, and her blood pressure was “a bit up and down”.

“I agreed reluctantly to go on hydroxyurea, just to get my blood counts down and to see if that made any difference,” said Sue.

“My understanding was that hydroxyurea could be quite good for controlling your blood counts, but it didn’t do anything about controlling possible disease progression to two other versions of MPN–very active PV and myelofibrosis (MF).

“One thing MPN patients are very interested in is the risk of disease progression and how they might minimise that.”

“It’s only a low risk but it’s there, and there’s really way no way of predicting who will progress. There’s still a lot that’s unknown.

“I was always very interested in interferon but any haematologists I spoke to in Australia at that time said the side-effects were difficult, and ‘you don’t want to be on it’.

“I was aware pegylated interferon was available in Australia on compassionate grounds, and knew efforts were being made to try and it on to the Pharmaceutical Benefits Scheme (PBS).

“At the time it was about $1400 a month… more than I wanted to pay.

“I was really grateful when Nathalie Cook (a MPN patient and advocate) was successful in her effort to get Pegasys on the PBS and I thought, ‘yes, I’d really like to give it a go’.

“As soon as it became available, I asked my haematologist to put me on it and I had to be assertive in my request. I was her first patient on it for MPN,” said Sue who had been on hydroxyurea for 18 months.

“Once I went on Pegasys, I was extremely relieved and surprised. I don’t think I’ve had any side effects and I haven’t had any headaches,” said Sue.

“It takes a bit of getting used to, injecting yourself, and I got advice and tips from other patients that was very helpful.

“I was able to live my normal life. It really didn’t impact me. And I feel incredibly grateful for that.

“In my case, it worked very effectively at a very small dose and I’ve actually been able to halve the dose. So, I only use it every fortnight and I’m trucking along quite well.

Sue Taylor and husband John
Sue with her husband, John, on their travels

“My bloods are all within normal range.

“I don’t want to sound as though I’m an advocate for it, because everybody’s got their own response to different treatments, but for me, it’s worked well so far.”

Sue’s been on Pegasys for more than two years. This includes a four-month break when she “had an episode” and ended up in hospital with a high fever and severe chest pain.

“We’re not sure if that was related to the Pegasys or not, but I’ve been back on it again for a year and it hasn’t happened again.

“In the course of that, I sought another opinion from a haematologist with more experience with interferon, and other medical specialists.

“I was very well looked after, and my current haematologist was very good at facilitating all that too.”

“And that haematologist, who I saw for a second opinion, looked over my full history and was suspicious that I may well have masked PV, which was interesting.

“I still have the diagnosis of ET formally but I’m not so worried about it now, so long as I’m on a drug that is keeping my haematocrit under control.”

“My haematocrit has been below 45 since I’ve been on treatment so at least I feel comfortable that any thrombosis risk is being managed.

“The other reason I was really keen to have an accurate diagnosis was that when new drugs come along or clinical trials, they usually have pretty specific criteria as to who can have them,” said Sue.

“Who knows what might come along in the future.

“There are some really positive results coming out of clinical trials into a new type of interferon alfa-2b, called ropeginterferon (Besremi®). It’s a slightly different formulation and is longer acting.

“It’s been tested on people with PV, and the results have been quite good as reported at ASH [the American Society of Hematology annual meeting] and in Europe at some haematological conferences.

Sue Taylor at the Mayo Clinic in Arizona
Sue Taylor when she attended the MPN patient conference in Scottsdale Arizona: “the Mayo Clinic is in the background”

Sue feels very fortunate her MPN hasn’t held her back in life “at all”. Her response to this “strange diagnosis” was to focus on having a healthy life and doing as well as she could by eating healthy food and controlling her weight.

She was already doing pilates and bushwalking, so she joined a gym and went several times a week for her cardio fitness.

“The joy of using your body and feeling strong and fit I found to be an unexpected benefit… a buzz. I felt really good,” said Sue, but she developed an ankle problem which has taken “some years” to get better, with “months and months” of rest.

“I’ve got severe arthritis in my ankle. That’s probably the worst thing that’s happened to me.

“It’s the inability to do what I love most, which is being physically active.

“I still do pilates and walk, but only on the flat,” said Sue who is careful with her diet.

“I figured that if you’ve got an ankle injury or knees or hips, keeping your weight at a good level is a good thing, and it also helps with your mental wellbeing.

“I eat more of the good stuff and less of the not-so-good stuff” said Sue.

That means more good carbs, vegetables and fruit, fish, small portions of meat, more beans, nuts and seeds, and not eating between meals. She still treats herself to a slice of birthday cake and dark chocolate, going for quality not quantity.

Sue Taylor in 2017
Sue Taylor, when she went to the MPN patient conference in 2017

Sue tends to think of MPN “as a chronic condition, like diabetes”.

“I’m focusing on doing what I can to maintain my general health and fitness.”

“People can be worried by MPNs being called ‘cancer’, which has the unfortunate effect of frightening people. I can understand why it’s called a cancer, but there are benefits for MPNs to be cancer, including cancer funding and getting more notice from doctors and researchers.

“I have never felt frightened of my diagnosis. My intellectual curiosity to find out more about MPNs is my way of taking control.

“I was given no information,” said Sue about when she was diagnosed.

“When I moved to my second haematologist and was in the waiting room of a big teaching hospital in Sydney, I found all the Leukaemia Foundation booklets. I was very excited to see the MPN one amongst the others. It gave me some basic information.”

Travelling is not so high on Sue’s agenda these days. She’s providing support to her elderly mother and has two grandchildren to enjoy time with, and one on the way.

“We’re a pretty close family, so we like to see as much of them as we can,” she said.

Looking back on her journey with MPN, Sue has realised it “takes time to adjust”. From her interaction with other MPN patients, she understands that everyone has a different experience with their MPN, and there is no “one size fits all.”

AL amyloidosis trials due to open this year offer “new hope”

AL amyloidosis trials due to open this year offer “new hope”

Dr Simon Gibbs at an international haematology conference in Boston, in 2019
Dr Simon Gibbs at an international haematology conference in Boston, in 2019

Two clinical trials will open later this year for newly diagnosed patients with AL amyloidosis with moderate to severe cardiac disease.

These studies will hopefully address a major unmet need, according to Dr Simon Gibbs, Director of the Victorian and Tasmanian Amyloidosis Service, and a founding member of the Australian Amyloidosis Network (AAN).

“The big challenge we have is that group of patients who have been diagnosed late with severe cardiac disease,” said Dr Gibbs.

“We know that, unfortunately, up to a quarter of these patients still die within six months of diagnosis.”

Dr Gibbs said the other 75% “often enjoy really good responses to treatment” and “we know that patients have very good outcomes if we get control the excess production of light chains quickly”.

“Not everyone responds as well as we’d like to our standard upfront therapy, VCD (Velcade®, cyclophosphamide and dexamethasone),” he said.

“Daratumumab is clearly an effective therapy to rescue patients who have poor responses to VCD, and the ANDROMEDA study proved that using daratumumab with VCD improves response rates.

“But we really need more rapidly effective treatments for patients presenting with advanced cardiac disease, or who don’t respond well enough to VCD.”

“We are hopeful two upcoming trials, the AFFIRM-AL (birtamimab) study and the CAEL-101 trial, will help address this unmet need, help to overcome early mortality, and may offer advances in patient quality of life and survival,” said Dr Gibbs.

Both Phase III global trials are looking at the standard therapy for AL–VCD–plus either birtamimab (previously called NEOD001) or CAEL-101. These drugs are monoclonal antibodies that target the amyloid deposits, and an aim of these studies is to clear the amyloid from affected organs.

Birtamimab was studied previously in the VITAL study. While the overall patient group in this trial did not significantly benefit with the addition of birtamimab to VCD, there was a strong suggestion that patients with advanced cardiac disease obtained the most benefit, and may have enjoyed better outcomes than the group that received VCD alone.

“One problem with the VITAL study was that there weren’t enough patients in the advanced cardiac group to be sure that birtamimab was beneficial, but the signs are good. So we are hopeful the AFFIRM-AL study will show a positive result,” said Dr Gibbs.

These two trials will look solely at people with advanced cardiac disease at diagnosis, to see if these drugs, which help to strip away the amyloid, have benefits for this group.

“We are always on the lookout to ensure our patients connect to the world’s best novel treatments and clinical trials,” said Dr Gibbs.

“The good news is that patient outcomes are improving overall.

“We’re finding that patients with mild to moderate disease at diagnosis generally do very well and tend to be living a lot longer.”

“Most patients will obtain a good remission from their AL amyloidosis.

“Patients are surviving much longer than 10-20 years ago,” said Dr Gibbs.

“This is because we now have access to newer, more active drugs like bortezomib (Velcade®), and lenalidomide (Revlimid®).

“We are also much better these days at choosing which patients will benefit from stem cell transplants, and daratumumab has recently been shown to be of significant benefit to many patients with AL amyloidosis, which is a very exciting advance,” he explained.

“In addition, there’s a greater understanding of medications that can help support the affected organs, and there are more amyloidosis centres of excellence around the world, so there’s more knowledge.”

Another trial will soon be available for relapsed AL amyloidosis

Dr Gibbs said a third trial, for relapsed/refractory AL amyloidosis, also “will hopefully be starting at the end of the year if all goes well”.

“It’s an Australian-French collaboration, which we are very excited about.”

Expert Series interview with Dr Simon Gibbs on all things ‘amyloidosis’

Expert Series interview with Dr Simon Gibbs on all things ‘amyloidosis’

Dr Simon Gibbs in Paris
Dr Gibbs at Gard du Nord Paris

Dr Simon Gibbs is a consultant haematologist (Myeloma/Amyloidosis Lead) at the Department of Clinical Haematology Eastern Health (Melbourne), Director of the Victorian and Tasmanian Amyloidosis Service, a founding member of the Australian Amyloidosis Network (AAN), and Honorary Senior Lecturer at Monash University. In this far-reaching interview, he discusses everything from the incidence, diagnosis and treatment of amyloidosis, to supportive care, quality of life, and how Dr Gibbs came to specialise in this field.

What is amyloidosis and how common is it?

Dr Gibbs describes amyloidosis as “a group of diseases where proteins within the body kink or misfold, then stick together abnormally and deposit in organs causing them damage. Once enough of these sticky misfolded proteins or amyloid ‘fibrils’ deposit in the organs, they can cause the organs to fail”.

“Amyloidosis is not as rare as we once thought it was. There are many types, but the two most common are AL and TTR,” said Dr Gibbs.

“In AL, the misfolded proteins are excessive amounts of light chains, which are part of the immune system and produced by the bone marrow.

“In TTR, the misfolded proteins are transthyretin, a protein mostly produced in the liver, but the amyloid fibrils mainly affect the heart.

“Unfortunately, both TTR and AL amyloidosis are under-diagnosed or diagnosed late. We know many patients will see several specialists over many months before the diagnosis is made.”

“We still have the challenge that amyloidosis can be difficult to diagnose.”

“Fortunately, in the last decade we’ve discovered there’s an easier way to diagnose TTR amyloidosis, by using a special bone scan. This has led to greater awareness of this disease, so patients are being diagnosed and treated earlier, and hopefully that equates to better quality of life and overall survival.”

Dr Simon Gibbs at Hong Kong Star Ferry
Dr Simon Gibbs on the Hong Kong Star Ferry.

And there’s more awareness of AL amyloidosis now than six years ago, when Dr Gibbs returned to Australia from the UK.

“AL amyloidosis is a disease of adults. We don’t see it in children, it’s unusual before the age of 45, and the incidence seems to peak in the mid-60s.”

According to a Queensland study, approximately 12 people per million are diagnosed with AL amyloidosis, and there is a slight male predominance.

In TTR amyloidosis, 85-90% of patients have wild type (or non-hereditary disease) and 90% of these cases occur in men, with the average age at diagnosis being 75-80 years.

In the 10-15% of people with of TTR that is hereditary, the disease affects men and women equally and is more likely to involve the nerves. This can cause numbness, pain or electric shock-like feelings in the feet, cramping of the legs, weight loss, bowel disturbance, and dizziness.

Dr Gibbs said TTR amyloidosis appears to be a disorder of ageing. In Japanese and Finnish studies that looked at autopsies of people aged 90 or older when they passed away, it was discovered that 25% of these people had amyloid deposited in their hearts.

“It seems that if we live long enough, we’ll probably all develop TTR amyloidosis!”

“We think there are about 7000 people with TTR amyloidosis in Australia, but this is a wild guess.

“Detection of this disease is definitely increasing. In 2016, we had one new referral a month to the Victorian and Tasmanian Amyloidosis Service, now we’re receiving one or two per week.

“In Melbourne at least, this disease is seen mainly in Caucasians, particularly of Italian heritage, and we don’t see it so much in people of Asian backgrounds.

“Interestingly, there seems to be a slight predominance in people who have been elite athletes in their youth,” explained Dr Gibbs.

“I have a number of ex-AFL footballers who have TTR amyloidosis.”

Dr Gibbs said a ‘red flag’, or warning sign, for TTR amyloidosis is any man aged over 60 who has had both his carpel tunnels released.

“So, if a man has had a carpel tunnel release operation on both wrists, our rule of thumb is that you should always consider that they are at high risk of developing TTR amyloidosis. If these men present with shortness of breath, unexplained weight loss, fatigue, or swollen ankles, they have TTR amyloidosis until proven otherwise, and they should immediately have a bone scan.”

“That’s one of the messages we are really trying to deliver now to cardiologists.”

One of the differences with TTR amyloidosis, compared to AL (which can affect almost any organ), is that typically TTR only affects the carpal tunnels, the heart, and spinal ligaments.

“Over 70% of TTR has had carpal tunnel syndrome, which usually develops 10-15 years before heart problems emerge. Many, especially ex-sportsmen, will also have had laminectomies or spinal surgeries in the past.”

Dr Simon Gibbs and others at AAN Amyloidosis 2019 meeting,
At the AAN Amyloidosis 2019 meeting, Simon Gibbs, second left, with Dr Fiona Kwok, Professor Angela Dispenzieri and Associate Professor Peter Mollee

Dr Gibbs wonders whether tissues in the body that have been used a lot are more prone to laying down TTR amyloid fibrils, such as the hands, back, and heart, and “sportspeople tend to use these a lot, but we really don’t know”.

“There are lots of unanswered questions and that’s one of them.”

But Dr Gibbs said the good news is that, over the last five to 10 years, the availability of medications that can slow progression of TTR amyloidosis has increased.

“The advantages of attending an AAN centre is access to drugs that you can’t get elsewhere, such as diflunisal, which, if tolerated is a good treatment for TTR, especially neuropathic disease; compassionate access programs for drugs like tafamidis; or clinical trials of newer therapies, such as patisiran or inotersen.”

And Dr Gibbs said trials of gene-silencing medications to reduce the production of TTR look particularly promising.

With other non-TTR hereditary forms of amyloidosis, Dr Gibbs expressed his frustration that there still were no specific treatments for those patients.

“Sometimes we put our patients on doxycycline – an old antibiotic – which may slow the misfolded proteins sticking together, so hopefully slowing the disease a little bit, but a lot more research in this area is desperately needed.”

Dr Gibbs highlighted the point that the amyloid proteins in Alzheimer’s disease are “completely different” to the amyloid proteins seen in AL or TTR amyloidosis, “so the risk of developing Alzheimer’s for someone with TTR or AL is the same as everyone else [in the community]”.


Dr Simon Gibbs at Medical and Scientific Advisory Group meeting
Dr Gibbs, centre front, at a Medical & Scientific Advisory Group meeting

How Dr Gibbs got into medicine, haematology… and amyloidosis

While at school, Dr Gibbs aspired to being in a profession “where you help people” but when his parents worried that medicine would be too much work, he considered being a lawyer or an accountant.

“I did work experience in a law firm but ran away from there thinking, “Oh my God, there’s no way I could do law!”.

Dr Gibbs didn’t think he was clever enough for medicine until he received his final school results.

“I started medical school and felt incredibly dumb because I went from being one of the bright kids in the classroom at school to being a very average student at university,” explained Dr Gibbs, but he persevered through the six years of medical school.

He trained at Melbourne University, his internship was at the Royal Melbourne Hospital, then he went across to St Vincent’s Hospital as a second-year junior doctor where his first rotation was in haematology.

“Medicine, as something to study, is very, very interesting and once I started seeing patients, it became a lot more rewarding.

“I worked under some amazing doctors. I was the junior resident to Andrew Wei, who was the haematology registrar at the time.

“Andrew has gone on to become Professor Wei, and is Australia’s leading expert in acute leukaemia.

“Andrew is just such a brilliant, brilliant doctor and mentor. He inspired me, so I decided to enrol as an advanced trainee in haematology at the Peter MacCallum Cancer Centre and St Vincent’s.

“I really enjoyed haematology for the fact that you really get to know the patient and you go on a journey with them, supporting them from diagnosis through often quite a few months of treatment, then hopefully remission and even cure.

“It is a very rewarding speciality, in my opinion.

“Haematology has always excited me because it’s a fast-moving field. It’s evolving. There’s a lot of research going on, so I always found it very interesting, and I’m a naturally inquisitive person.”

Dr Gibbs, out and about in Nice
Dr Gibbs, out and about in Nice while attending a meeting there.

As a junior haematology registrar, Dr Gibbs had a patient with AL amyloidosis.

“It was pretty clear to me that no one really knew back then how to best treat what was thought to be a very rare disease, and I had a patient die a pretty horrible death on me, and I thought, ‘Oh, God. That’s awful’.”

Then Dr Gibbs had an opportunity to complete his final year of haematology training in Cambridge in the UK. His boss at the time, Professor Nandurkar, now Director of Haematology at the Alfred Hospital, suggested that he return to Australia from the UK with a ‘niche’ or new skill not readily available in Australia. At Cambridge, Dr Gibbs saw more amyloidosis patients.

“I heard about this National Amyloidosis Centre [NAC] in London. They compiled these terrific reports on patients, very informative, and I thought, maybe that’s my niche,” said Dr Gibbs.

He went down to London and met with the Director of the NAC, Professor Philip Hawkins, and was offered a job on the spot.

“He said, ‘not a lot of people are interested in amyloidosis’.”

Dr Gibbs enjoyed his two-year amyloidosis fellowship so much, he stayed on at the NAC for an additional 2½ years! Dr Gibbs admits that, not only were the doctors he worked with there great mentors, but the opportunities in London, and the ability to travel regularly to amyloidosis meetings all over the world, made him stay on longer than originally planned.

He then moved to northern England, to lead the huge myeloma service at the Manchester Royal Infirmary for more than two years. While there, he set up the first satellite clinic for the NAC.

Dr Simon Gibbs walking in Scotland
Dr Simon Gibbs walking in Scotland

Returning home and setting up Australia’s third Amyloidosis Service

Dr Gibbs wasn’t sure he could “put up with English winters” for the rest of his life, so when he was approached by Victoria’s Eastern Health to help establish their new myeloma service, he jumped at the opportunity to return home. But he ensured that the job allowed for setting up a dedicated amyloidosis service – the first in Melbourne.

Dr Gibbs returned to Australia in 2014 and founded the Victorian and Tasmanian Amyloidosis Service in close liaison with the two existing amyloidosis clinics in Australia, at the Princess Alexandra Hospital (Brisbane) and Westmead Hospital (Sydney).

“In 2016, our three services met and agreed not to compete but to collaborate, so we set up the Australian Amyloidosis Network,” he said.

“The idea was that we would join forces to help enhance awareness of amyloidosis, services and supports to patients, and to attract new treatments and clinical trials to Australia.

“At the time, Australia was being overlooked for clinical trials in amyloidosis.”

“We were delighted when, in 2018, the Fiona Stanley Hospital in Perth agreed to join the AAN, under the leadership of Dr Hasib Sidiqi who’d just returned from a fellowship in amyloidosis at the prestigious Mayo Clinic in the U.S.

“Since Hasib joined, I think we’ve been pretty successful in bringing important international clinical trials to Australia. Fortunately, we have some terrific colleagues in Adelaide also.”

Since forming the AAN, the two leading Prothena studies in AL amyloidosis – VITAL and PRONTO – as well as Janssen’s ANDROMEDA study, the largest ever clinical trial globally in AL amyloidosis, were offered to Australian amyloidosis centres.

“With the exception of Greece, Australia had more patients per capita than any other country enrolled on the ANDROMEDA study, and it meant we could give daratumumab to some our patients that we otherwise couldn’t do.

“Then the Eidos AG10 study was our first clinical trial in TTR amyloidosis. This drug looks very promising, and we await the initial results of this study, which hopefully will be released in early 2023.

“We now have four really good TTR trials running in Australia” which, Dr Gibbs said, “is just amazing”.

Details of these trials are available on the AAN’s website.

Three AL amyloidosis trials are expected to open later this year.

Importance of supportive care

“I think supportive care can be just as important in many cases as the chemotherapy itself,” said Dr Gibbs.

“One of the pieces of advice I give patients is… if you’re getting a symptom that’s really upsetting or bothering you, really jump up and down about it, because we do have treatments that can help most symptoms.

“A haematologist is very good at giving chemotherapy, but we know that AL amyloidosis patients have more complex needs than myeloma patients because of their organ involvement.

“I suggest to patients, many of whom have three or four specialists… always ask all your doctors to copy each other in on letters and reports, and always bring a copy of your medications to your consultation.

“An amyloid specialist acts like a conductor of an orchestra. We will often be the central person for the cardiologist, the local haematologist, the kidney specialist, and the neurologist to communicate with about the coordination of the patient’s care.

“Sometimes we doctors aren’t always good at communicating regularly and effectively with each other, and so we might not necessarily know of changes to medication or results of scans ordered by other doctors.”

Quality of life advice

Dr Gibbs said, for a lot of patients with AL amyloidosis, poor appetite is a major problem.

“Normally, when we start eating, the stomach relaxes so it can fill up with all the food from a full meal. In amyloidosis, this reflex is lost or is sluggish. So when the stomach doesn’t relax, patients feel full more quickly.

“We call this ‘early satiety’ or ‘gastroparesis’ (paralysis of the stomach).

“Patients usually have a good breakfast, barely anything for lunch, and skip dinner because half their breakfast is still sitting in their stomach by the time dinner comes around.

“One of the easiest things to do for AL patients who say, ‘I’ve lost a lot of weight’, ‘I’ve no appetite’ is put them on a ‘prokinetic’ drug. These medications help push food through the stomach, so patients can eat a bit more.

“Medications such as domperidone (not Dom Pérignon!) or metaclopramide can really help improve patients’ appetites and maintain their weight,” said Dr Gibbs, and he puts at least half of his patients on domperidone.

“And all of a sudden, patients can go from only having two small meals a day to maybe one full meal and another two half meals. They eat a bit more, meaning they have a bit more energy, less chronic fatigue, and they stop losing weight. This can be a big psychological boost for patients, as well as a physical one.

“It’s such a simple thing, starting domperidone. It’s very helpful and can make a big difference to quality of life.”

If you are losing weight, Dr Gibbs said starting dietary supplements like Sustagen, and seeing a dietitian, can be helpful.

“If you’re struggling to maintain a good weight, whatever you’re eating, make sure it’s full of lots of calories.

“Try to eat things that are high in protein and calories that are easy to digest. Minced meat is easier to digest than a steak, so things such as cottage pies and Bolognese sauces can be good. They are easier to swallow, easier to pass down through to the stomach, and easier to digest.

“Try drinking cordial rather than water, or maybe have a soup or protein shake, and add a spoonful of honey to your tea.

“And try to avoid of lot of bread. Many people say bread is quite difficult to digest. It sits in the stomach for a long time and doesn’t move through easily.”

Dr Hawkins and NAC fellows
Professor Philip Hawkins, centre, with Simon Gibbs and National Amyloidosis Centre Fellows in the UK.

The ALIGN study

Nutrition is a poorly studied area in amyloidosis, according to Dr Gibbs, and the Victorian and Tasmanian Amyloidosis Service has begun a clinical study, called the ALIGN study, for newly diagnosed patients.

It’s looking at their dietary history, liver size, and the transit time of food through the stomach (through gastric emptying studies).

“We’re collecting information about weight, diet, and conducting quality of life and supportive care screens.

“The idea is to really look at diet and quality of life and the use of prokinetics, such as domperidone, and see how much of a difference they make and who benefits the most. Anecdotally, I think it makes a huge difference, but we are in the process of looking at this more scientifically.

“We want to conduct these investigations, if possible, before treatment starts.”

As it is still early days regarding results, Amyloidosis News will report back on the findings of this ongoing study in two years.

Dealing with neuropathy

Peripheral neuropathy can be caused by the amyloidosis itself or, in some circumstances, from treatment, such as with bortezomib (Velcade®).

“Once intermittent neuropathy symptoms became more regular, we need to question, ‘what are your light chains and have we achieved a good enough response?’ so we can decrease the dosage of bortezomib to control these symptoms or even consider a treatment break,” said Dr Gibbs.

“Often we’ll give six cycles or roughly six months of treatment. If you obtain a 90% response within the first cycle or two, but you’re starting to develop neuropathy by month three or four, we can probably reduce your bortezomib by half or space it out to fortnightly dosing, if you’ve got to where you need to be.

“There’s no point suffering from constant leg pain or dizziness,” he said.

“Various therapies can help treat peripheral neuropathy symptoms such as electric shock feelings or pain in the legs.

“Lyrica® and Endep® are medications that help to decrease the sensitivity of the nerve endings. They can cause a bit of drowsiness, so most patients take these at night before going to bed, which helps with sleep.

“And, start on a low dose and slowly build up to levels that are going to be helpful. The other thing is to be patient! These treatments can take up to six weeks to kick in and work.

“When starting any new medication, think about taking the first few doses at night, because if you develop side-effects, hopefully you’ll be asleep when you get them, so they won’t feel as bad. Then your body starts to get used to the medication,” said Dr Gibbs.

“And for general pain, two tablets of good old Panadol will decrease the intensity, but you have to take it regularly, don’t wait for the pain to hit. If you take it when the pain has already started, it’s not going to work.

“If patients develop cramps, magnesium, and quinine, which is found in tonic water, are quite good.

“For dizziness when you stand up, sometimes a medication called midodrine can be very helpful.”

The three ‘Ds’ for fluid retention – diet, drinking, and daily weigh-ins

If you suffer from a lot of fluid retention, Dr Gibbs said it was important to cut out all the salt from your diet.

“Speak to your doctor about whether you should be on fluid restriction and how best to manage your diuretic medication (water tablets).

“Weighing yourself first thing every morning, after emptying your bladder, can be a helpful way to monitor your fluid retention,” he said.

“But as with everything, it’s always good to discuss these things with your doctor.”

Knowing your light chain levels is important

Dr Gibbs suggests patients with AL should be aware of their light chain levels at diagnosis and monitor these levels during each month of treatment. This involves a simple blood test.

“Patients with AL amyloidosis should ask their haematologist, ‘what was my light chain level at the start of treatment?’ Then ask what their light chains are every month during chemotherapy. Then you’ve got an idea of how you are responding to treatment.

“What we need is for that light chain level to decrease by at least 50-75%, absolute minimum, and optimally you’d want to decrease it by 90-100%.

“The main thing to bear in mind is that it often takes a few months to get a really good response,” said Dr Gibbs.

A simple blood test for earlier diagnosis

When Dr Gibbs was asked if he had a ‘holy grail’ of amyloidosis diagnosis and treatment, he said, “I would love a simple blood test that you could very easily do that would tell you, ‘yes, this patient is making amyloid’, or not, to help speed up diagnosis.

“The second holy grail would be a safe and effective medication that would remove the amyloid from the body quickly, easily, and without side-effects.

“Another unmet need is a more coordinated approach to patient care from various specialists,” he said.

“The AAN is collecting a series of amyloidosis experts in each organ speciality in each state to whom we can direct our patients when they say, ‘look, I’m struggling to find a good neurologist who knows about amyloidosis’ or ‘I’m struggling to find a good cardiologist’.

“One of the things the AAN is trying to do is to have a shared care model whereby we’re all working together; you have a haematologist who’s giving the day-to-day chemo, but you also have an amyloid specialist who’s supporting that local haematologist, to ensure you’re receiving the best supportive care as well as the best chemotherapy or TTR medication, and have access to clinical trials that may be beneficial.

“I do that a lot with patients in rural Victoria and Tasmania,” said Dr Gibbs.

What Dr Gibbs would do if he was diagnosed with AL amyloidosis

“I’d want to go and see a haematologist who was very experienced in amyloidosis, someone who is part of or closely connected to the AAN, or who attends amyloidosis conferences.

“If I received my treatment locally with an experienced haematologist, I’d still consider being seen at an AAN centre, at least initially, to ensure we had the correct type of amyloid diagnosed and the best supportive care mechanisms in place, and to see if there were any clinical trials that were applicable to me.

“I would want a specialist who sees me regularly for the organs that are involved with the amyloidosis. So, if I had, say, kidney, heart, and nerve involvement, I would want an experienced cardiologist, nephrologist, and neurologist looking after my heart, kidneys, and nerves respectively, who communicates regularly with my haematologist/amyloidosis specialist. However, I acknowledge that this can sometimes be a challenge.

“Being informed can be helpful. The Leukaemia Foundation produces a wonderful booklet (Amyloidosis – A guide for patients and families). So, I would read that booklet, and I’d review the AAN website, which is There is the Leukaemia Foundation Facebook page for amyloidosis patients for support and it can be helpful for all sorts of different reasons. The ‘Amyloid Awareness’ cartoon on YouTube is also very interesting.

I would definitely attend any educational workshops about amyloidosis, to help understand the disease, and to keep up-to-date with the latest information and ideas about supportive care about this complex disease.”

The AAN is running Patient and Carer Educational Workshops on Saturday, May 8 in each capital city. For those unable to attend a face-to-face conference, the meeting in Melbourne will be live streamed and recorded online for later viewing. Check the AAN website regularly for details.

Amyloidosis in the future

Dr Gibbs is encouraged by the breakthroughs that have occurred over the last 10 years in the field of amyloidosis.

“Collaboration within Australia has made a huge difference in increasing awareness of the disease, leading to earlier diagnosis and treatment, and improved outcomes for patients,” he said.

“And international collaboration with research and clinical trials has accelerated novel drug discovery and accessibility within Australia.”

By working together and communicating regularly, Dr Gibbs believes everyone benefits.

If you are interested in making a donation in support of amyloidosis research, please contact the Leukaemia Foundation on 1800 620 420 or

Diagnosed finally at 33 – Keith’s now in remission

Diagnosed finally at 33 – Keith’s now in remission

Keith and Felicity Moore
Before going to Melbourne for his stem cell transplant, Keith Moore proposed to Felicity

Keith Moore was “ridiculously young” to be told he had AL amyloidosis and it took nine months before he finally got that diagnosis.

He’d just turned 33 and had begun an adult apprenticeship as a mechanical engineer after 14 years as a butcher.

“It was a totally different field; in something I love. It was fantastic,” said Keith, a professional speedway racing car driver.

But six weeks into that new job, Keith started getting ill. At first, he couldn’t get on top of a series of colds and flus. Then he got a painful burning sensation on the skin of his feet and chest, which felt on fire.

Keith Moore in hospital
It took Keith Moore nine months to get a diagnosis: “I wish I’d had an earlier diagnosis.”

“I wasn’t sure what was going on, so we went to the doctor,” said Keith, now 36, of Murray Bridge, an hour north of Adelaide. His partner at the time, Felicity Czech who is now his fiancé, went along with him.

“My resting heart rate was abnormally high, about 90-95 beats per minute. That was a bit strange.

The doctor put Keith on an ECG machine and when this showed an abnormality, he was referred to a cardiologist.

Over the next nine months, Keith saw the cardiologist every four to six weeks and he also “bounced around between GPs, because they all seemed to think there was nothing wrong with me”.

“We were beyond frustrated as no one seemed to want to listen,” said Keith.

“It felt like I was being treated like a drug addict wanting drugs.”

“My heart rate was quite fast, my blood pressure was low, but the rhythm was fantastic, and I didn’t have a temperature.”

Keith developed other symptoms too, excruciatingly painful feet which meant, after working all week, he’d spend all weekend on the couch. He had a tingling feeling in his feet too and had trouble “going to the toilet”.

“I was sweating at night profusely,” said Keith and this meant getting up to change the sheets and his clothes during the night.

“I couldn’t sleep, then during the day I would sit down and fall asleep instantly for a bit, and numerous times I almost fell asleep driving the car home.”

He often got bloodshot eyes, vomited every day and night, was short of breath, and had shooting pains through his body, “like somebody just put a knife into me”. And he couldn’t drink alcohol.

But the biggest concern for Keith, an extremely fit, well-built guy who described himself as “80kg of pure muscle”, was the weight he lost over three months–20kg.

“I was nothing but skin and bone.

“I knew in the back of my mind there was something seriously wrong with me, but I’ve always been the sort of person that never got sick. I suppose I was in a lot of denial.

“I was sure they’d find out what was wrong, and I’d be right in a couple of weeks.

“It was a very strange and scary time.”

More than a decade earlier, when Keith was 21, he’d been diagnosed and treated for Wolff-Parkinson-White* syndrome.

“It’s quite a common thing. I’d had a heart ablation for that and was fine. Still to this day, I don’t have a problem with it at all.”

His cardiologist couldn’t work out what was wrong with Keith, so he referred him to another cardiologist. Keith had another “heap of tests” including an MRI scan of his heart. This picked up “some sort of infection” in his heart and he had a heart biopsy.

“We went in for the results six weeks later, and he said, ‘oh, you’ve got amyloidosis’.

Keith Moore with speedway car
“I had a brand new car and I took it for its first race, and won!” said Keith, a professional speedway racing car driver

“We had no idea what that was, and he didn’t explain it to us very well. He pretty much just said, ‘we can fix it with chemo, but I’m going on holiday, so I’ll see you in six weeks’.

“In my current state, I would not have lasted another six weeks,” said Keith.

He and Felicity said they “did a bit of Dr Google reading, which you really shouldn’t do”.

“What we read at that time was, ‘you have about 12 months to live’.

“That shot us down a fair bit, so we quickly made a GP appointment to double check our findings and we could tell by his face that this was not good, and he said we should talk to our families and make a plan.

“I had to tell my young children that Dad was going to go in about a year. It was horrible,” explained Keith who has three children, now aged 17, 13, and 11.

Scrambling, and feeling like everyone had already given up on him, Keith jumped on Facebook seeking help. He found a support group and immediately posted, “this is what I’ve got. I’m quite scared. I don’t know what to do”.

“A lady rang me. She gave me a bit of a back story on amyloidosis. Her husband had passed away 10 years prior.

“She said, ‘get on to this guy, Simon Gibbs, he’s Australia’s leading expert’.

“I emailed Simon the next day and said, ‘please help. I’m 33. This is what I’ve got’. It was a Thursday. He rang me straight away and said, ‘can you come to Melbourne on Monday?’.

“I said, ‘yep, we’ll be there’, so my father and my partner booked tickets and we were off on the plane to Melbourne on Sunday, and on Monday, Simon took one look at me and stuck me in hospital to start chemo the next day.”

“We thought this would be a 24 hour round trip!”

At the time, Keith didn’t realise how close he was to dying.

“I didn’t want to have chemo and when we asked about other treatments available, Simon’s reply was, ‘I don’t think anyone wants to have chemo’.

Keith Moore Felicity and daughters
Keith, dressed for the speedway, with Felicity and his two youngest children

“He pretty much said, ‘if I don’t give you chemo, you won’t last two weeks’; that’s how frail I was.”

“Simon told me amyloidosis had come a long way in 10 years. It had been a death sentence, but today more people are surviving with new treatments, and CAR T-cell therapy is coming which is meant to be the new greatest thing.

“Amyloidosis is quite rare. Most people who have it are 60, 70, 80 years old, so to find it in somebody 33 years old is just ridiculous.”

“I believe I’m Simon’s [Dr Simon Gibbs] youngest patient he’s ever had.

“We have a very good relationship, Simon and me. I said to him, ‘look, no bulls..t. Don’t sugar coat it, tell me how it is. I need to know what’s happening. If you do that, I’ll guarantee I’ll get through it’,” said Keith.

In Melbourne, Keith started chemotherapy and arrangements were made for him to see a local haematologist back in South Australia, and a week later, he flew home and continued the medication Dr Gibbs had given him.

“I finally got to see the haematologist [in Adelaide] two weeks later and she did the same thing, she took one look at me and stuck me in a hospital. She didn’t think I had a chance of surviving, but Simon’s response to her was – ‘he’s young, he can do this’.”

Keith continued the treatment for six months, then went back to Melbourne to see Dr Gibbs.

“He said, ‘right, another three months-worth of treatment’.

The issues Keith had during his 12 rounds of VCD**, began in the first month when he was rushed to hospital in a lot of pain, having not had a bowel movement for five days, then during the last cycle of chemo, he got a urinary tract infection and a cold.

Keith loves a bit of salt but people with amyloidosis need to limit their salt intake so he paid the price with a lot of fluid retention in his legs and in his chest, which affected his breathing.

“Other than that, I didn’t get sick and stayed completely healthy,” said Keith.

“We got the light chains down as far as we could until the treatment stopped working, then he [Dr Gibbs] said, ‘right, you’re fit, you’re healthy, you’ve put on weight’–I was back to 80kg–‘let’s do it’.

Keith went back to Melbourne to have his stem cells collected in the leadup to having an autologous stem cell transplant.

“While I was in hospital, Simon had a patient who had just had a stem cell transplant come and talk to me. He was fit and healthy and back to work. “He was actually a mechanical engineer like I am, which was fantastic.

“We related to each other a fair bit. He was an older guy, in his 50s, which is still quite young for amyloidosis. We had a great chat and he told me what he went through.

“That was really helpful… to see it can be done. That was a big turning point.

“He was pretty confident I’d be fine, which was the hope we needed.

Keith Moore in hospital larking
Keith larking about during treatment

Three weeks later, at the end of May 2019, Keith had his transplant at Box Hill Hospital and a week later Felicity had to return home to the children and work.

During his five weeks in hospital, Keith almost died from an infection that ended up being associated with his PICC line, which was removed.

Then, after spending another week in Melbourne, at a hotel***, “to double check nothing was going to go wrong”, Keith and his dad took two days to drive home.

“I spent another seven weeks recovering at home before I went back to work full-time.”

“My family, the doctors, everyone, all told me off and said I went back to work too early,” said Keith, but he was determined.

“My work was fantastic. When I explained what was happening to me [after Keith’s diagnosis] and that treatment would take 12 months, they organised for my apprenticeship to continue and gave me 12 months off work. My job would be waiting for me when I returned.

“I had almost 12 months off to the day.”

Since returning to work in August 2019, Keith has gone from strength to strength.

During his transplant, Keith had problems keeping his food down, and for nine months he continued to struggle with nausea. But the peripheral neuropathy in his feet, caused by the amyloidosis, has “pretty much gone”, along with his former fatigue, and now he’s “the perfect weight.

“I eat fine. I drink fine. I go to the toilet fine. My heart rate has come down.

“I’m probably 95% back to where I was. I do have a little bit of nerve damage, but not too much. I still get a little bit tired every now and then. I have to make sure I drink water consistently and am constantly hydrated. And my vision was affected. Now I wear glasses all the time.”

Keith’s not on any maintenance medication and his bloods are in the normal range.

“It’s a bit of a miracle to be honest.”

During December 2019 and January 2020, Keith’s light chains started to rise again, and arrangements were put in place for him to have lenalidomide (Revlimid®). This took some time, and when Keith finally got access to the treatment, in April, COVID-19 had struck.

“When I called Simon, he said it was probably not a good idea to take lenalidomide as it would lower my immune system. He decided to do another test on my light chains. If they were high, I would have to take the lenalidomide, but if they were low, we’d hold off and keep an eye on them.”

It turned out, however, that Keith’s light chains had gone down on their own.

“They went back to normal and have been normal ever since,” he said.

“I am currently in remission. We try not to use that word, and Simon even dropped the word ‘cured’ once. He said, ‘we don’t like to say it, but we think you’re cured, but we won’t say that ever again’.”

Keith has a blood test every six to eight weeks “just to make sure”, and everything has been in the normal range for 12 months now, with no maintenance therapy whatsoever.

Keith Moore and Dr Simon Gibbs
Keith Moore with Dr Simon Gibbs’ youngest AL amyloidosis patient

Reflecting on his experience with amyloidosis, Keith said, “it is hard to talk about. It’s quite scary what we went through and the fear of it coming back is still there, and that will never go away unfortunately”.

“We know it’s there. We know that one day we’ll probably have to deal with it [amyloidosis] again.

“We try to put it out of our minds and just keep on moving and trying to live a normal life,” said Keith, who still has more stem cells “on ice, waiting for me, if I ever need them again”.

“We’ve got a whole new perspective on life. We do things differently; we don’t take things for granted now. We take the time to appreciate everything.

“We don’t go out and party hard like we used to, we sit back and relax and look at the world now instead.

“We spend more time with the family, try not to work as many long hours, don’t worry about the small stuff.

“We’re getting married as well.”

“I proposed before I went over to Melbourne for the stem cell transplant,” said Keith, and the wedding is being planned for next year.

Keith, who had to give up racing for three years due to his illness, recently returned to the speed track. Some of his friends took his race car away to re-do it.

“Some of my friends took my car away to re-do it, so I didn’t have to worry about it.

“While I was going through treatment and without me knowing, they got together with my friends, family and sponsors, and built me a brand new top-of-the-class race car,” said Keith.

Unfortunately, it didn’t quite get finished–the business of the people who took on the project, took off and they ran out of time. So when Keith got back from Melbourne, he picked up where they left off.

“I had a brand new car and I took it for its first race, and won!”

He put a myeloma ribbon decal on the bonnet and under the words, “Amyloidosis awareness”, to promote the two diseases.

“I also have myeloma,” said Keith.

“When we went over to Melbourne for the transplant, the Leukaemia Foundation helped out, paying for a bit of accommodation in the hotel while I was there, which was fantastic.

“And we got a heap of information from them, which was really good. They posted that out to us,” said Keith, and in 2019 he took part in the Leukaemia Foundation’s Light the Night event.

When it comes to advice for others with amyloidosis, Keith is adamant: “Don’t read the internet. That’s number one”.

“Although we did Google ‘the best diet for someone with amyloidosis’. The Mediterranean diet was recommended, and we stuck to it – fish twice a week and lots of berries.

“For nine months, I ate a punnet of strawberries every single day.”

Keith wishes he’d had an earlier diagnosis.

“The hardest part was not knowing and not getting answers for such a long time,” he said about those nine months.

“We hope this story helps others by lifting the spirits of those suffering with amyloidosis and myeloma and those caring and supporting them,” said Keith.

“And hope lies with this story, which proves that its ass can be kicked.”

* Wolff-Parkinson-White (WPW) syndrome is a rare congenital heart disorder involving irregularities in the electrical system of the heart. Treatment may involve medication, a procedure known as ablation, or, in rare instances, an electric shock may be used to restore a normal rhythm.

** VCD is a combination of bortezomib (Velcade®), cyclophosphamide and dexamethasone.

*** The Leukaemia Foundation helped out by paying for this accommodation.

Leanne’s been treatment-free for five years

Leanne’s been treatment-free for five years

Leanne and Ted Pitman
Leanne and Ted in 2015 when they made the decision together that Leanne try stopping her CML treatment

“Yeah, let’s give this a go. Let’s get these horrible drugs, that have saved my life, out of my system and see what happens.”

That was the decision Leanne Pitman and her husband, Ted, made together back in mid-2015 after her haematologist, Associate Professor David Ross, talked to her about stopping her CML treatment.

At first, she was “very scared”.

“I hadn’t heard of anyone else doing it, so it was a little bit scary not knowing what would actually happen,” said Leanne, 60, of Adelaide.

During the discussion, she was reassured that she would be monitored very closely–in fact, for the rest of her life–and if there was evidence of CML reappearing, she could restart her tyrosine kinase inhibitor (TKI).

“So that was part of the understanding when we decided to come off the medication… I knew it was there to go back to if anything happened,” explained Leanne about the option of restarting treatment.

She immediately stopped taking the nilotinib (Tasigna®) tablets she had taken religiously every day for five years. Prior to that she had been on imatinib (Glivec®) since her diagnosis with CML just before Christmas in 2006, aged 46,

Leanne Pitman with parents Coralie and Donald
Leanne with her parents, Coralie and Donald Neave, who live with her in the house she and Ted bought in Adelaide

when she was living in regional South Australia.

(Read about Leanne’s early experiences with CML – her delayed diagnosis and debilitating side-effects of treatment)

The key reason Leanne chose to attempt treatment-free remission (TFR), under the supervision of her haematologist, was the extreme bone pain, fatigue, and other side-effects she had lived with for nine years.

“I started on Glivec and was on that for quite some time, about five years,” said Leanne, and she responded well to imatinib.

“I got to zero BCR-ABL on Glivec quite quickly, but I had a lot of trouble with side-effects. I was an absolute mess. I reckon I would have been in hospital at least once a month with it.

“Nausea was pretty bad to start with, but I seemed to manage that.

“Mostly the side-effects were bone aches. In the end, I couldn’t walk without a walking stick, I would be in that much pain continuously, vomiting from the pain. It was just really bad,” said Leanne.

“I was on Endone, Oxycontin, Panadeine. I was continuously taking painkillers, all the time.

“I can remember, when I was on Glivec, I was taking 18 tablets in the morning.

“At that stage I was still running a seven-day-a-week café.

“I’m very thankful that my daughter was in business with me, and I had some very good staff to help look after the café when I’d end up in hospital.”

At the time, the Pitmans were living at Penola, 400km from Adelaide.

“One of the hardest things, obviously, were the trips up to Adelaide all the time,” said Leanne about her regular appointments with her haematologist there.

These were initially monthly, then two-monthly, before being every three months.

“That was really hard, especially with my husband who was a truck driver. He’d have to take time off all the time,” said Leanne about Ted who had to drive her to and from Adelaide for her medical appointments.

“I couldn’t drive myself. I couldn’t drive any long distances at all.

They’d head off early in the morning and Leanne would still be her pyjamas so she could sleep on the trip.

Pain management lead to a change in therapy

Leanne was on so many painkillers that she was referred to a pain clinic in Adelaide where she was given a script for a different pain medication. When she went to fill it at Penola, the pharmacist said it would cost hundreds of dollars.

Leanne and Ted Pitman
Leanne and Ted Pitman: “I live 400km from my husband. Fortunately, we’ve got a very good relationship.”

“He said he had something the same but not that brand,” said Leanne.

“Almost immediately the pain stopped. It was a miracle, and I remember handing in all my other painkillers at the hospital, because I didn’t need them.”

Leanne said, “it was fantastic”, she was just taking imatinib and the new drug… but not for long. After her next blood test, she got a call from her haematologist.

“He questioned me as to why I wasn’t taking my Glivec.

“I remember so clearly saying, ‘I swear on the lives of my children, I have not missed any of my medication’.

“Anyway, I had to go back to Adelaide again, and we worked out that the new pain medication wasn’t exactly what I had been prescribed and had counteracted the Glivec.”

As a result, there was no evidence of imatinib in Leanne’s blood and her leukaemia level had risen.

After this incident, Leanne was able to change her CML medication to nilotinib, and her side effects weren’t as bad.

“The pain came back but it wasn’t as severe, and the fatigue wasn’t as severe.

“I tolerated it [nilotinib] a lot better and I never had to go back to using the walking stick,” said Leanne.

Moving back to Adelaide was a necessity

She continued making her three-monthly trips to Adelaide until 2013 when she moved back to Adelaide, and the Leukaemia Foundation provided her with some financial support.

“In the end I had to sell my café,” said Leanne.

“It got to the stage, with the frequent trips to Adelaide and there was no doctor in Penola and having a locum meant having to go in an explain myself every time to get medication, that we decided it would be better for me to move to Adelaide permanently.

“I live 400km from my husband,” said Leanne.

“Fortunately, we’ve got a very good relationship. We talk every night on the phone.

Leanne Pitman at AMCR 2012
Leanne, who has been an active fundraiser for the Leukaemia Foundation, took part in the Aussie Muscle Car Run twice

“When he gets the opportunity to come to Adelaide, he will, and he tries to come up for family events because the rest of our family now lives in Adelaide as well, or I try and get down there to him.

“It’s only been in the last two years that I’ve actually been able to drive the 400km without being in immense pain.

“Ted and I bought a large house [in Adelaide] and my parents moved in with me, so I look after them a bit, and our son and daughter and our three beautiful grandchildren are 10-minutes away.

“So if anything happens to me, or anything happens to them, we’re close together.”

And, in a couple of years, when Ted retires, he will re-join Leanne and the family in Adelaide.

The lead-up to treatment-free remission

“I had a lot of trouble getting doctors to understand what was going on with me, because this was something new, saying I had bone pain,” said Leanne.

“I was on the CML Facebook pages and I wasn’t the only one going through bone pain. Others were going through the same thing.”

Then, in July 2015, Leanne’s haematologist had a conversation with her and Ted about stopping her CML medication.

“Because my BCR-ABL1 had been zero for so long, many years,” said Leanne.

When she decided to try TFR, it was just days before going on holiday to Darwin to visit a girlfriend, and her first query was, “do I take it [the nilotinib] with me?”.

Then, because she still had “a fair bit of nilotinib”, at least a month’s worth, she wondered, “do I give it to someone else, because of the cost?”.

“I was thinking surely David [Ross] would have someone who could use it.

“Even though it was unopened, apparently you can’t reuse medications,” said Leanne, who ended up throwing out her leftover nilotinib a couple of years later when it was out-of-date.

Leanne has had no change in her blood test results since stopping nilotinib more than five years ago.

Leanne Pitman at WGS 2013
After driving 500km to support her friend in World’s Greatest Shave in 2013, Trish Crabb cut off Leanne’s ponytail
Ted shaving Leanne Pitman's hair at WGS 2013
Then Ted did the deed with the shaving shears

“I’m still zero in treatment-free remission.”

“I’ve had other specialised blood tests,” she Leanne who had consented to her blood samples being used for research.

“I was asked to participate in these other blood tests that had to be done on a certain day and the results took a lot longer.

“What they found, when looking deeper, is that I still have CML cells deep in my blood,” said Leanne, who was told, “they’re just sitting there”.

“I’ve done two of those tests and both times the CML cells have been there.

“I’m quite aware that if anything ever happens, there’s always the medication to go back to and I know that will control it.”

For Leanne, that’s very reassuring.

It’s five years since Leanne went on TFR and she still has a lot of side-effects.

“I still have the pains in my legs. Fatigue’s the worst, but I get on with my life and live it the best I can.

“I’m on the TFR Facebook page and it’s quite upsetting when you’re watching people and it’s, ‘oh no, blood levels have come back up. I have to start medication again’.

“That’s always in the back of my mind every time I have my blood tests.

“The last time I saw David [Ross], because it’s been five years, he seems to think it would be very unlikely now that it would come back, but you just never know.”

Leanne said she doesn’t give coming out of remission a lot of thought anymore.

“But I still say to people, because of my pain and fatigue, that I’m a leukaemia patient.”

Visits to her haematologist have dropped back to once a year, but she still has blood tests every three months, and this will continue for the rest of her life.

Looking back, Leanne thinks going on TFR was “a good decision”.

“I’m not on as many drugs, I’m a lot better off now as far as the bone pain, and I think I’m coping a lot better.”

Her advice to others regarding TFR is, “give it a go, because it gives you a break off medication, and the medication’s always there for you to go back to. That was what made our decision so much easier.”

Leanne is a great supporter of the Leukaemia Foundation, actively raising funds by taking part in the World’s Greatest Shave and Aussie Muscle Car Run twice, and she’s been an ambassador and has held Light the Night events at four different locations over the years.

Expert interview series: Dr Susan Branford on molecular monitoring and drug resistance in CML

Expert interview series: Dr Susan Branford on molecular monitoring and drug resistance in CML

Professor Susan Branford is better known internationally than here in Australia where she heads a diagnostic lab in Adelaide, has research interests in CML, and is an NHMRC Research Fellow. Her work on the importance of molecular response in CML has been widely recognised and includes the International CML Foundation Prize in 2016 for outstanding contributions to the improvement of CML treatment in emerging economic regions, and the International Federation of Clinical Chemistry and Laboratory Medicine Distinguished Award in 2017 for significant contributions in molecular diagnostics.

Professor Susan Branford’s work on molecular monitoring and drug resistance, although largely behind the scenes, has underpinned many Australian and internationally significant developments in CML over the last 20 years.

Professor Susan Branford in the lab
Professor Susan Branford in the lab

The pathway to her current position as Head, Leukaemia Unit, Genetics and Molecular Pathology at SA Pathology, Centre for Cancer Biology wasn’t conventional. She started as a lab technician who worked in clinical chemistry for many years.

“That gave me a really good grounding in some of the key elements required to generate good diagnostic tests, which is what we are doing here in the lab now, as well as research,” said Dr Branford, also Professor, School of Pharmacy and Medical Science, at the University of South Australia.

In 2000, she took the opportunity to move to a new department–Genetics and Molecular Pathology–where her role was to develop methods using a new technique, real-time quantitative PCR* in various cancers. She worked with haematologist, Professor Tim Hughes, who had set up PCR when he was at Hammersmith Hospital in London.

“My role was to develop a technique and to start to monitor patients with chronic myeloid leukaemia, which we did. At that time imatinib [Glivec®] was first being tested,” said Dr Branford about the original, first generation tyrosine kinase inhibitor (TKI).

“After a few years of developing this method and being very interested in the research I was doing, Tim [Hughes] said, ‘look, I think the work you’re doing is at a PhD level, why don’t you apply to do a PhD?’, so I did.

“I’d already published papers at that stage and even though I didn’t have a primary degree, the university looked at my credentials and said ‘yes’ to my application, based on my publications and relevant background.”

Introducing molecular monitoring to the international stage

Susan Branford with lab staff
Professor Branford, second on the right, with leukaemia lab staff in the RNA extraction area

Dr Branford had an opportunity to participate in some exploratory research in patients who were treated with imatinib.

“Until imatinib was available, CML patients were either treated with interferon, which most patients couldn’t tolerate and only a few responded to, or patients had an allogeneic bone marrow transplant,” she said.

“Then imatinib, which is a targeted therapy, changed everything.”

“From the first trials, it was clear that patients were going to have very good responses,” said Dr Branford.

“Tim [Hughes] told Novartis that we had a method to monitor patients and we were able to perform exploratory molecular analyses for Australian and New Zealand patients enrolled in the IRIS international trial, that started in 2000.

“This trial enrolled over 1000 patients and was the first trial of newly diagnosed CML patients treated with imatinib.

“We worked with colleagues in London and Seattle who also had monitoring methods set up using real-time PCR for patients with CML. These labs performed the molecular analyses for the other patients enrolled in the IRIS trial. But our methods were all slightly different, which meant our results didn’t align. So we worked to standardise the results, and this was the first attempt to align data for CML patients generated by different labs.

“The trial protocol required that molecular analysis was only commenced once patients achieved a complete cytogenetic response.

“But we were lucky enough to get support to test all of the Australian and New Zealand patients at three-monthly intervals. This proved to be really informative because we monitored patients more intensively than a lot of the other patients on the trial,” she explained.

“We found that the achievement of a certain molecular response correlated with very good outcomes and the data was published in 2003,” said Dr Branford.

“Then we followed those patients who became resistant to imatinib, looking for their mechanisms of drug resistance. That’s really how it all started.”

Significance of Leukaemia Foundation funding support

The overall aim of Dr Branford’s research is to understand why some patients with CML don’t respond to therapy, given that most patients do extremely well.

“Patients can be treated with imatinib, the first generation drug and the least potent, and have very rapid responses. Some patients may eventually be able to stop therapy and maintain treatment-free remission,” she explained about a typical CML patient journey.

“But we know that some patients have a delayed response. By using molecular monitoring, we found that values very early into therapy are highly predictive of how patients are going to respond.

“A lot of our work is focused on trying to understand and to predict why some patients do well and why some patients have a poor response.”

Susan Branford at CML meeting Bordeaux
Prof. Branford presenting at a CML meeting in Bordeaux (France)

Dr Branford, Professor Hughes, and Dr Deborah White received funding from the Leukaemia Foundation in 2008 that contributed to research with the primary goal of understanding the mechanisms of resistance and how to overcome this resistance to improve outcomes.

“At that time, we were very focused on mutations in BCR-ABL1. BCR-ABL1 is the primary genetic mutation that causes CML, and mutations in this fusion gene cause drug resistance. We were able to develop a very sensitive method to detect these mutations. We had some good publications from that work where we were able to show that low level mutations are clinically relevant.

“Any bit of funding we get means that we can do some analysis, even if it’s preliminary. We find these great preliminary results and we feed that back into our next grant application. It’s all been a fantastic support,” said Dr Branford.

Predicting treatment response

“We started off looking at BCR-ABL1 at diagnosis and found there was no predictive information; it didn’t matter what level you started with; it was what happened after treatment.

“By three months, if patients had a very rapid decline, they were going to do very well.

“We’ve always tried to find out what’s going on at diagnosis and it’s really starting to come together after many years of using new technology and looking outside of BCR-ABL1.

“We’re at quite an exciting spot.”

“We’re using new genomic and molecular techniques –whole exome sequencing**, or whole transcriptome sequencing–where we look at every gene at diagnosis.

“We did a pilot study that took us many years. We looked at patients who had the best responses and those who had the very worst responses. We found additional genomic abnormalities in some CML patients at diagnosis in addition to BCR-ABL1.

“These were mutations that are found in other types of leukaemia; in acute myeloid leukaemia and acute lymphoblastic leukaemia.

“Our study started in 2011 but even as far back as 20 years ago, scientists had detected the occasional mutation found in a highly mutated gene, like TP53.

“It wasn’t until the new sequencing technology came along that we could look at everything, and that we’ve really started to find these mutations.”

Dr Branford said the research has since been extended to an expanded cohort of CML patients, not just those with very poor or very good responses to imatinib. We are studying patients enrolled in the TIDEL II study, which was set up by Dr David Yeung and run out of Adelaide in conjunction with the Australasian Leukaemia & Lymphoma Group (ALLG). The results of that study were published in Blood in 2015. Blood is the top-ranking journal that publishes data on blood cancers.

“So far, in our preliminary work, it holds up that if patients have a mutation at diagnosis, then it puts them at a higher risk of treatment failure.

“PhD student and haematologist, Dr Naranie Shanmuganathan presented our preliminary data in early December [2020] in an oral session at the American Society of Hematology (ASH) meeting, which was a virtual meeting last year.

“We tested the diagnosis samples of patients where we know their outcomes; we know which patients did well and which patients did poorly.

“We’ve looked at the genomics at diagnosis of about two-thirds of the patients so far and have found that having these mutational events at diagnosis is an independent predictor of poor outcome.

“At a live question time after Dr Shanmuganathan’s presentation, one of the questions was, ‘when is this going to be available in the clinic?’.

“That was quite exciting for us, to hear that there is interest from around the world.”

“There is still a lot of work to do. We need to find out if the poor risk conferred by mutations at diagnosis can be overcome with more potent inhibitors.”

Dr Branford said the next step now is to go back and test the tissue samples (usually peripheral blood) of other CML patient cohorts–those treated with the more potent inhibitors such as nilotinib (Tasigna®) and dasatinib (Sprycel®) as their first line of therapy–to see what their outcomes have been.

“That could be quite useful,” she said.

“If we find that a patient has a particular mutation at diagnosis and is treated with a certain drug that reduces the risk of treatment failure, then that could be really important. It could be practice changing in terms of helping clinicians decide the best drug to give at diagnosis.

“Our aim is to identify those patients who will do really well on the standard dose of imatinib, which is a safe drug, whereas the more potent inhibitors (nilotinib and dasatinib) have some toxicity and cardiovascular risk associated with them, so the patients who have those drugs need to be carefully selected.

“But that’s another year or so off until we get those results.

“We’ve got patient consent for this work, it’s just a matter of funding.

“Getting funding is becoming harder and harder and, unfortunately, there may be a time when we just aren’t able to pursue the things we would like to do, based on our preliminary data, because we just don’t have funds.”

Prof. Branford interviewed by the European Hematology Association
At ASH 2016, Prof. Branford was interviewed by the European Hematology Association

Retrospective analysis using archived tissue samples

For a lot of this research, Dr Branford uses existing samples that have been collected and stored for many years in Adelaide.

“Patients with CML are routinely monitored for BCR-ABL1, and we do a lot of the molecular analysis for Australian clinical trials.

“We’ve got about 700 patients who we’ve followed in clinical trials.

“It’s a great resource,” she said.

“We correlate the data with the BCR-ABL1 values we’ve collected over time.”

Groups around the world are finding that tissue banks of stored patient samples, where the response to treatment is known, can provide a wealth of information.

“It’s a very nice retrospective analysis,” said Dr Branford.

“One of the initial mechanisms of drug resistance we found were mutations that occurred within the BCR-ABL1 gene itself, in the drug-binding site.

“Again, with this rich data source, we were able to go back, track, and correlate the emergence of these mutations with drug resistance.

‘We’ve moved on from there and are now looking more broadly at other mutations and other genes,” she said.

Several other groups around the world developed molecular monitoring techniques and established these rich data resources at around the same time; the Hammersmith in London; in Germany; and Jerry Radich’s group in at Seattle in the U.S.

World first trial for asciminib has opened

Hopefully, new samples will be added to the CML tissue bank in Adelaide from the 100 participants who are expected to enrol in a new national study that opened in late 2020.

“I think this is the first clinical trial in the world treating newly diagnosed patients with a new drug, called asciminib,” said Dr Branford about the ALLG CML13 study, also known as the ASCEND trial, run from Adelaide.

Asciminib, previously known as (ABL001) is another drug that targets BCR-ABL1, but it is different because its activity is very specific.

“It has limited off-target activity, so has limited toxicity. We’re very excited to be able to test and treat patients with asciminib as their first line of therapy.”

But Dr Branford said her research group doesn’t have the necessary funding to test these patients at diagnosis.

“We keep applying to various funding bodies to get the money to do the testing. The patients will all be consented to do the test, it’s just dependent on if we can get some funding,” she explained.

“This trial might recruit very quickly because, at the moment, this drug is not available outside of a clinical trial.”

Data on asciminib was presented at ASH in a late-breaking abstract session on the results of a large randomised Phase III trial, called ASCEMBL, for patients who had failed prior therapy; up to three different therapies.

“This drug met its primary endpoint, meaning it was superior to the other drug that was used in the trial – that’s very exciting,” said Dr Branford.

“It’s now gone in for fast track approval to the FDA [in the U.S.] as the second line therapy as a monotherapy.”

Dr Branford said we will have some idea how well patients respond to asciminib very early in the ASCEND trial and there is a treatment intervention timeline.

“By three months, if the patient hasn’t reached a certain level of BCR-ABL1, then the study has built in some treatment intervention at that stage.

Susan Branford at HAA meeting 2015
Speaking at the HAA annual scientific meeting in Adelaide in 2015

Investigating the effect of mutations on therapy response

While Dr Branford heads a diagnostic lab, her focus is research, which involves grant writing and paper writing [for submission to journals], and involvement in clinical trials.

“We’ve worked with Novartis over a number of years. They have an interest in these mutations that cause resistance.

“Over the last few months, we have been testing samples of patients enrolled in the ASCEMBL trial at the time just before they start their asciminib; we’re looking at what mutations they have, and we’re starting to get data from this clinical trial.

“We will do an exploratory analysis, to see the effect of these cancer gene mutations on response to asciminib. This will be a companion analysis to that in the TIDEL II trial,” said Dr Branford who, since 2018, has been writing up the trial methodology and has performed validation studies.

“We’ve got a huge amount of data and we’re analysing the last of our data for the TIDEL II study. We’ll do the statistics on that, and that will be the next paper we work on.”

Rolling out molecular testing across the globe

Dr Branford considers her greatest contribution to science is developing the molecular techniques and being involved in rolling out the test globally.

“It is now accepted that this is how patients should be monitored,” she said.

“Over the last decade, once we demonstrated that there was a clinically relevant reason for doing molecular analysis, labs have taken this up. We had to work hard as an international community with collaborators to standardise methods.

“It took many, many years… a lot longer than we thought, because the technique is quite complex and lots of things can lead to variability.

“Now it’s routine that all labs offer molecular testing for CML, whereas if we look back five or six years ago, that wasn’t the case.

“It is much harder in undeveloped countries and we’ve been working with commercial groups, including Cepheid, which developed an instrument called the GeneXpert.

“Again, this has been a work in progress over the last decade.

“GeneXpert is a very rapid cartridge-based method that’s used in a lot of labs in places like Africa and India, where patients can’t access drugs unless they have a definitive CML diagnosis.

“GeneXpert has come to prominence in the COVID era because this instrument is being used for rapid COVID testing, but it also does rapid BCR-ABL1 testing.”

The importance of molecular monitoring

In the first molecular monitoring study Dr Branford did, in the IRIS trial, she found that if patients reached a certain level of BCR-ABL1 after 12 months of therapy, they were essentially protected from disease progression.

“It’s now known as a safe haven, and it’s got its own term, it’s called a major molecular response,” she said.

“It’s the equivalent of a three-log reduction from the diagnosis level. That was the first time that this was found to be an important response.

“Now, in most clinical trials, the primary endpoint is the achievement of a major molecular response and if that can be achieved within 12 months of therapy these patients will have a very good outcome.

“A lot of groups then looked at earlier time points and we’ve now found that if patients reach a BCR-ABL1 ratio of 10% at three or six months, then this has prognostic information. If patients don’t reach these levels, we know that those patients are at risk of treatment failure, disease progression, or even death.

“We now have molecular milestone values at three, six, and 12 months, and these are now our decision points.”

Dr Branford said that in 2013, international recommendations for monitoring patients with CML, published by the European LeukemiaNet, for the first time recommended that molecular milestone values are used for treatment decisions.

“Very early molecular monitoring is important because it can determine whether clinicians should change therapy so that patients have a chance of achieving an optimal response,” she said.

“If BCR-ABL1 values are greater than 10% at three months, the recommendation is to confirm the result by doing another test very rapidly. And if it’s still greater than 10, that’s a bad sign. That’s when the recommendations mandate a change of therapy. Otherwise those patients are at high risk of disease progression. It’s become very important.”

Greatest unmet need in CML

Dr Branford thinks the greatest unmet need in CML is finding appropriate therapy for patients whose disease advances to a rapidly fatal blast crisis. This only occurs in a small number of patients now.

“There are some patients who progress very rapidly,” she said.

“We recently had a young person here who was diagnosed in the chronic phase, started standard therapy, and unexpectedly went straight into blast crisis. Very sad. The patient will have an allogeneic transplant.”

“Tyrosine kinase inhibitors are not effective for patients with disease progression and there is no other effective drug therapy,” said Dr Branford.

“Their best chance is to have chemotherapy, to ablate the leukaemia, then go on to have a transplant. Fingers crossed for this most recent patient.”

Between five and 10% of patients fit into this category, depending on the drug they start their treatment with.

“There’s less progression if patients start with the more potent inhibitors, but these are associated with greater toxicity. There’re pros and cons, and these are the issues their clinicians are dealing with at the time of diagnosis; what’s the best drug for their patient?”

When Dr Branford finishes all the current preliminary work looking at diagnosis, she hopes to focus her research on this group of patients.

“Maybe, if we can introduce rapid genomics at diagnosis, we can work out what are these mutations that are leading to this very rapid progression.

“Maybe it will identify those patients who perhaps need a more potent inhibitor, and they should start to look for a [bone marrow] donor very early,” she said.

“If we can identify a mutation, like IDH1, which we’ve seen occasionally in CML, and which we know occurs in acute myeloid leukaemia, we know there are inhibitors for that.

“As more and more drugs are developed that target specific mutations, there may be effective treatment for these patients.”

Ongoing developments in CML

Dr Branford said that, in addition to the asciminib trial and the research using genomics, a “very exciting area of research is trying to understand how we can pick patients who are going to be successful when they stop therapy; that is, patients with treatment-free remission”.

“I’ve been fortunate enough to be involved in international patient advocate groups because of our international connections,” she said.

“Following on from our work, and other groups’, where we are looking at genomics in CML, Tim and I formed the International Genomics Alliance, which was launched in 2018, to eventually pool all of our data, and we are working closely with patient advocates.

One over-arching group, called the CML Advocates Network, has connected 125 CML patient groups worldwide, and is working with academics and pharmaceutical companies to work out goals and spread word of the latest research findings.

Dr Branford worked with two international patient advocates who are both in treatment-free remission and who helped review her most recent grant application.

“It’s becoming more and more important that we work closely with patients, and that they review our grant applications,” she said referring to what is acceptable to the patient community, such as the level of drug toxicity.

“There are some drugs that are highly toxic,” she said.

“Modification of our grant applications based on feedback from patients is going to be important to improve overall outcomes for patients.”

* Polymerase chain reaction (PCR) is a technique used to amplify small segments of DNA because significant amounts of a sample of DNA are necessary for molecular and genetic analyses.

** Whole exome sequencing sequences the 1.5% of the whole human genome that codes for proteins. Whole transcriptome sequencing sequences the RNA and can measure gene abundance.

Latest ALLG clinical trial recruiting for CML

Latest ALLG clinical trial recruiting for CML

A new clinical trial run by the Australasian Leukaemia & Lymphoma Group* (ALLG) is currently open to eligible people with chronic myeloid leukaemia (CML).

MoleculeCML13 – leading doctors, Dr David Yeung and Professor Tim Hughes

The CML13 trial is evaluating the most appropriate treatments for CML patients and the purpose of this important clinical Phase II trial is to evaluate the efficacy of asciminib in newly diagnosed patients with chronic phase  CML.

Asciminib (previously known as ABL001) is a novel allosteric inhibitor of BCR-ABL that has demonstrated good tolerance and efficacy in CML patients who are resistant or intolerant to the currently available tyrosine kinase inhibitor (TKI) drugs.

This trial is open to recruitment at the following sites:

Victoria – Peter MacCallum Cancer Centre

New South Wales – Concord Hospital

South Australia – Royal Adelaide Hospital.

More locations to open over coming months.

For more information on this and other current clinical trials in CML, visit the ALLG website, or speak to your treating haematologist.

* The ALLG is the only not-for-profit collaborative clinical trial group in Australia and New Zealand delivering research projects focused on blood cancers. The ALLG’s purpose is to achieve better treatments and better lives for people with AML and other blood cancers. ALLG clinical trials are taking place at 93 accredited hospital sites and cancer centres across the country and more than 800 physicians and haematologists, nurses, scientists, and professional support staff are ALLG members.

Living with blood cancer and pets

Living with blood cancer and pets

For many people living with blood cancer, their pets are an integral part of the family. They would be lost without the love and companionship pets add to their lives.

Your furry friends often can stay by your side during and after blood cancer treatment providing you consult with your treatment team and take the appropriate measures to reduce your risk of infection.

Read our top tips on how to safely care for your pets while undergoing and recovering from treatment.

Lyndell Wills with her dog Meggs
Lyndell Wills, who was diagnosed with MDS in 2015, with her dog Meggs.

Talk to your treatment team

After receiving a blood cancer diagnosis, speak with your treatment team about your pet and your routine for taking care of them. Not all pets pose the same risks, and not all blood cancer treatments do either. Your treating team can provide advise on how to safely interact with your pet throughout your blood cancer treatment.

Understand the risks

When undergoing chemotherapy or a bone marrow transplant, there will be times where you are immunosuppressed and more susceptible to an infection. Avoid bites and scratches at this time and if your pet plays rough it may be necessary for your family or friends to look after them until your immune system recovers.

Visit your vet

Consult with your veterinarian to ensure your pet is up-to-date with its immunisations and booster shots. Ask whether any of the vaccinations are ‘live’ and check with your treatment team before these are given to your pet. Your vet can also prescribe medicines to prevent heartworm, fleas and ticks in dogs and cats.

If you have a cat, have it tested each year for feline leukemia (FeLV) and feline immunodeficiency (FIV) viruses. While these viruses cannot infect humans, they can weaken your cat’s immune system which can put them at risk of other infections that can infect humans.

Make hygiene a priority

Wash your hands after petting, caring for, touching or feeding your pets, and remember to wash your hands before taking medicine, handling food or anything in your kitchen.

Several illnesses can be spread through pet faeces and urine. Have someone else clean up after your pet or clean the litter box, and make sure it is not kept in the kitchen or anywhere you consume food. If you must do the clean-up, wear disposable waterproof gloves and wash your hands afterwards.

Always keep your pet’s sleeping areas as clean as possible and ensure your pet does not come into your bed while you are recovering from treatment.

Keep your pet healthy

Try to keep your pet on your own property or indoors to minimise their risk of picking up an infection from other pets and animals. Cats that go outside and hunt birds or small rodents are at risk of getting a parasitic infection called toxoplasmosis. While this infection tends not to make the cat sick, it can be very serious, even fatal, for a human with a weakened immune system.

Try to avoid dog parks and walk your dog on a leash in places where they won’t encounter other animals of unknown health.

Adopting a pet during treatment

While it is not usually recommended, some people do choose to get a new pet while undergoing treatment. If this is a choice you make, it is best to adopt a healthy pet that is at least 12 months old and to have it checked by your vet. Puppies and kittens tend to ‘play rough’, bite, and scratch, and have more ‘accidents’ that need cleaning up during toilet training.

Animals to avoid during treatment

It is best to avoid contact with birds, reptiles, rodents, and other exotic pets when undergoing blood cancer treatment. These animals are common carriers of salmonella and other rare but serious diseases. Salmonella can cause diarrhoea, skin infections, and other serious viruses which can be lethal for people whose immune systems are weakened. This germ can live for some time on surfaces and objects that an affected animal has touched, which means it can be transmitted without you handling the animal.

If you do choose to keep these animals as pets during treatment, ensure you follow the precautions above when handling, feeding, cleaning up after them or handling objects the animal has touched.


Real stories about living with blood cancer and pets

Lyndell’s passion for her pets keeps her strong

Lyndell Wills is a bone marrow transplant recipient, has survived myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) and is mum to chickens, Sox the cat, and dogs, Meggs and Molly.

Lyndell Wills with her red dogs
Lyndell Wills with her red dogs, Meggs, top and Molly, bottom

She was diagnosed with MDS in 2015 with it progressing to AML in late 2017.

“I was basically neutropenic from my first diagnosis, but things really ramped up when I got the AML diagnosis and was told I would need chemotherapy and a bone marrow transplant,” said Lyndell, who lives on Lake Macquarie (NSW).

“When we travelled to Sydney for my treatment, my husband and I had to leave the chickens, cat, and two dogs behind to be looked after by friends and family.

“For the first four weeks in hospital I was constantly asking my treatment team when I would be able to see them again.

“We did speak about bringing them to the side entrance of the hospital for a quick visit, but I decided that would just confuse them, with the different smells and environment.

“Throughout my whole treatment I kept photographs of my animals up on the walls of the hospital room, so they were with me in some way and gave me strength.”

Lyndell Wills' photos on her hospital wall
Lyndell Wills covered her hospital window with photos she’d taken of African animals and her pets to get her through treatment.

Lyndell’s transplant, from an unrelated matched donor, was in December 2017.

“I stayed at the Westmead Leukaemia Foundation Patient Accommodation Centre for my three-month recovery,” said Lyndell, mum to daughters, Shannon, 20, and Zoe, 16.

‘’That was the most challenging time, having to be away from my two daughters and pets for so long, but we did manage a few short visits back home when I started feeling better.

“The chickens are obviously recognised as one of the high-risk animals for infections.

“We spoke to the haematologist who ran through how we can best manage that, and I certainly got out of cleaning chicken poop out of the cage for a good three years.

“But I would still sit and watch them, I just loved that when I was in the middle of treatment and feeling my weakest because they’re so busy, inquisitive, and very entertaining.”

Having dogs has also provided Lyndell with the motivation to get out and about again.

“Some days you don’t really feel like getting out of bed and want to bury yourself under the covers,” said Lyndell.

Lyndell Wills with her dog Meggs
Lyndell Wills had many pets, including her dog, Meggs, when she was diagnosed with blood cancer 

“But then you see that look in their eyes willing you to take them for a walk.”

“I now try and do something with the dogs most days. Some days it’s a shorter walk than others but it’s better than staying couped up all day.”

Lyndell encourages people to speak with their treatment team and practice good hygiene when handling their pets.

“You’ve just got to be sensible. After patting or feeding the animals, I always get up and wash my hands,” said Lyndell.

“If you’ve got an open wound, don’t let the pet near it, and avoid scratches.

“I would also highly recommend seeing a psychologist and talking about this adjustment to your lifestyle for the good of your health.

“You don’t realise what a big impact it can have on you mentally and the decision to keep pets, while it was non-negotiable for me, some people may need to work through that choice and understand what the best approach is for them.”

Lyndell also runs an online support group called, Transplant Tribe, for those who have had, or are planning to have, a bone marrow transplant, as well as their family and friends. Find out more at


Pets ‘like therapy’ to Barb through treatment

Barb Vezos with her cat Kitty
Barb Vezos with her cat, Kitty

Barb Vezos, who couldn’t imagine life without her beloved pets, prioritised hygiene and health so she can continue taking care of them safely.

Diagnosed with acute myeloid leukaemia (AML) in 2015, Barb underwent chemotherapy and a bone marrow transplant from an unrelated matched donor. At the time of her diagnosis, she was a single mum to two boys, and had four pets to care for.

“One of my dogs went with my sons to their uncle’s place, and my neighbours fed both my older dog and cats for me while I stayed at the Clem Jones-Sunland Leukaemia Foundation Patient Accommodation Centre during my nine-month treatment in Brisbane,” said Barb, from Beaudesert (Queensland).

“I’m so grateful for their support, it was really important to have my pets taken care of by people I know and trust.

“Unfortunately, one of the cats and dogs passed away while I was going through treatment which was really devastating…but I still returned home to Kitty the cat and my dog, Daphne, who were ecstatic to have me back.”

Before going home, Barb she spoke to her treatment team about caring for her pets safely and ensuring she minimised her risk of infection.

Barb Vezos with her dogs
Barb Vezos with her dogs; Sydney, an Akita X, and Daphne, a staffy

“I did have the option to re-home them, but I decided to just see how I went with them and if I ended up with an infection or allergies, then I would reassess,” explained Barb.

“My cat is really good, she’s not scratchy and she does her own thing most of the time.

“My dog, Sydney, was a new addition at the end of 2017. Both dogs are content to just sit by me, they don’t have to be all over me. Sometimes I look into their eyes and just know, they know what’s going on – they are so gentle.

“They can come inside, but I tend not to let them on the couch and bed now, and I am constantly washing my hands after touching and feeding them.”

Barb still remembers the week between chemotherapy and her transplant when she went home and could spend time with her pets.

“I think that was the most relaxed I had been the whole year. To just have that constant companionship was like therapy to me,” said Barb.

“I don’t know how to explain it, but the pets give me a sense of peace and are the best company in the world.

“I’ve always had animals and I couldn’t imagine my life without them.”


American Cancer Society. Infections and Pet Safety [Internet] 2020

Leukaemia & Lymphoma Society. Pets and Cancer: How to Care for Yourself & Your Furry Friends During Treatment [Internet] 2020

Memorial Sloan Kettering Cancer Center. Returning Home After Your Autologous Stem Cell Transplant: Pets [Internet] 2019

Cleveland Clinic. Preventing Infection After Bone and Marrow Transplant [Internet] 2019

Very Well Health. Keeping Pets When You’re Diagnosed With Cancer [Internet] 2020

Children’s Cancer and leukaemia Group. Children with cancer and pets [Internet] 2014

The importance of molecular response in CML

The importance of molecular response in CML

By Professor Susan Branford PhD, a medical scientist with the Department of Genetics and Molecular Pathology, Centre for Cancer Biology, SA Pathology and the University of South Australia and University of Adelaide.

My PhD research in biomedical science involved assessing people with CML to determine if monitoring the level of disease during therapy using a molecular marker could predict treatment outcome.

I also investigated the reasons for drug resistance that occurs in a small number of patients.

Key levels of molecular response on the International Scale 
Key levels of molecular response on the International Scale

The tests I developed are now incorporated into routine patient monitoring along with the other blood tests a person with CML has on a regular basis after diagnosis.

CML is a genetic disease. A change in the structure of DNA within cells leads to the formation of a new gene that does not behave normally and causes CML. The new gene is formed from the fusion of two different genes and is called BCR-ABL1.

BCR-ABL1 is a molecular marker that can be measured during therapy. Importantly, a blood sample is required to measure BCR-ABL1 levels rather than bone marrow, the collection of which is associated with greater discomfort for patients.

In the past, there was a greater need for people with CML to have bone marrow biopsies to diagnose their disease and to monitor their response to therapy. Bone marrow collection is still necessary at diagnosis and is a very important part of patient management.

In Australia, however, molecular monitoring of BCR-ABL1 during therapy, using a blood sample, has largely taken over from bone marrow testing. The advantages of molecular testing include a shorter time for the result to be ready, and the test is 300-1000 times more sensitive for detecting low levels of leukaemia, compared with cytogenetic testing.

Professor Susan Branford
Professor Susan Branford

Our laboratory has been monitoring BCR-ABL1 levels in patients with CML for a long time and was one of the first laboratories in the world to develop this technique.

We monitored patients in early clinical trials for imatinib – the first drug that was truly effective for most CML patients and since then there have been many clinical trials of different and more powerful drugs.

All the trials have consistently shown that the molecular test can provide very useful clinical information for the prediction of response to drug therapy, and many labs around the world are now performing the test.

The molecular technique is not easy for new labs to develop and BCR-ABL1 values can vary from lab to lab. To overcome these differences, about 10 years ago it was decided that all labs adopt a common way to report the results, so a BCR-ABL1 value is similar no matter in which lab it is tested.

Working with many labs around the world, we developed a set of recommendations for the testing procedure and BCR-ABL1 values are now reported on an international reporting scale. This has improved the quality of the results.

A panel of experts recommended that BCR-ABL1 values reported on the international reporting scale be used to determine if a patient is responding well to therapy or if a change of therapy is necessary to improve response.

BCR-ABL1 levels indicate molecular response
BCR-ABL1 levels indicate molecular response

The critical timepoints to assess response is at three, six and 12 months of drug treatment. A value of 10% at three months, 1% at six months, and 0.1% at 12 months is an optimal response, and no change of therapy is necessary. Most patients reach these levels.

A small number of patients develop drug resistance and the main reason is a change in the DNA sequence of the BCR-ABL1 gene that can stop the drug working properly.

A rise in BCR-ABL1 level can indicate that drug resistance is occurring. When a rise occurs and the doctor suspects relapse, a blood sample can be used to check for a change in the DNA sequence of BCR-ABL1. The haematologist can then decide whether a change of therapy is necessary.

There is still a lot we don’t know about CML. At the time of diagnosis, we can’t identify those patients who will fail their therapy. But technology is rapidly advancing, and over the next 10 years, we hope to more thoroughly examine and understand the molecular changes that occur, which will lead to improved treatment and better outcomes for all patients.