Ruxolitinib and risk of non melanoma skin cancer

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A study published in the January 2024 issue of Blood authored by 28 haematologists and researchers throughout the UK titled ‘Outcomes and characteristics of nonmelanoma skin cancers in patients with myeloproliferative neoplasms on ruxolitinib‘ raises serious concerns that patients on ruxolitinib should be aware of the risk of non melanoma skin cancers. The study followed 90 patients (median age 73) who had developed NMSCs whilst on ruxolitinib therapy.

There is an article on the MPN Research Foundation website in the US  which contains a link to the full study HERE.

“Non-melanoma skin cancers in ruxolitinib-treated patients with myeloproliferative neoplasms (MPNs) behave aggressively, with adverse features and high recurrence. In our cohort, mortality from metastatic NMSC exceeded that from myelofibrosis,” the UK study authors report.

Ruxolitinib can be effective in reducing spleen volume and symptom burden as well as potentially prolonging survival in responding patients. “However, benefits need to be balanced against potential toxicities…” the authors suggest.

“Our study highlights the aggressive nature of NMSCs in ruxolitinib-treated patients with MPN, the importance of counseling patients about the risk of skin cancer before starting ruxolitinib, and a requirement for close dermatological monitoring on treatment.”

Optimal MF management following diagnosis of NMSC remains uncertain, according to the authors. “Stopping ruxolitinib may result in MF (myelofibrosis) symptom flare and potentially increase the risk of disease progression, and it is not yet clear whether ruxolitinib cessation (or switching to an alternative JAK inhibitor) impacts NMSC outcomes. Consequently, if a patient develops an NMSC while taking ruxolitinib, the risks and benefits of each treatment option need to be carefully weighed and discussed with the patient, acknowledging the uncertainties alluded to above, before deciding whether to change therapy.”

“Larger, prospective collaborative studies are needed to better understand NMSC risk and outcomes in ruxolitinib-treated patients with MPN, the report concludes, as are similar evaluations of NMSC risk in patients with MPN treated with other JAK inhibitors.”

 

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Australian cancer atlas 2.0 reveals geographic impact of cancer diagnosis across the country

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Image 1: Professor Peter Baade launching the Australian Cancer Atlas v2

In partnership, Cancer Council Queensland (CCQ) and Queensland University of Technology (QUT) have released their new version of the Australian Cancer Atlas, an online cancer map revealing startling new geographical patterns across Australia.

Latest results from the Australian Cancer Atlas 2.0 shows the impact of cancer varies substantially depending on where Australians live. While the patterns vary for different cancer types, where there are differences, the consistent pattern is that Australians living in regional and remote areas experience poorer survival than those living in urban areas.

Cancer Council Queensland’s Professor Peter Baade says Cancer Atlas 2.0 provides unique information about the extent and characteristics of these geographical patterns, which is crucial for motivating the next step of understanding why these disparities exist.

“There is substantial evidence that, when it comes to cancer, where you live really matters. Our research demonstrates the disparities faced by Australians living in regional and remote areas have not improved over time,” said Professor Baade.

QUT Centre for Data Science Director, Distinguished Professor Kerrie Mengersen says this tool is critical in helping define rural and regional health care planning.

“Now we have the data, the next step is understanding the ‘why.’ Once we do that, we can make informed changes to reduce these differences in cancer rates. By using the Cancer Atlas along with the new Australian Cancer Plan, we can give policymakers, advocates, and communities the tools to make better health outcomes for all Australians.”

The Leukaemia Foundation is using the Australian Cancer Atlas to enhance their research to better understand the impact of blood cancer across the country.

Tim Murphy, General Manager Blood Cancer Partnerships at the Leukaemia Foundation says the Australian Cancer Atlas is a valuable tool to ensure the right resources are in the right places.

“The Australian Cancer Atlas will assist the sector to explore the essential data needed to address blood cancer more effectively and provide crucial insights to help us improve how we support affected communities in Australia,” said Mr Murphy.

“The cancer atlas will bring us closer to understanding blood cancers reach and impact and enable us to enhance our research and tailor our interventions more precisely to shape future healthcare strategies and to fight blood cancer head on.”

The MPN AA is delighted to showcase version 2 of the Cancer Atlas of Australia which includes updated data on myeloproliferative neoplasms (MPNs).

MPN incidence and MPN patient survival are mapped in detail across the country.  Across all cancer types, the consistent pattern is that Australians living in regional and remote areas experience poorer survival than those living in urban areas. MPN survival data is no different. Cancer Council Queensland’s Professor Peter Baade explains that “The atlas shows which areas have above-average risk factors for cancer, which areas have low screening or testing rates, higher rates of cancer diagnoses, and which areas have poorer survival rates.”

The MPN AA continues to highlight disparities in MPN incidence across the country. We believe some differences may be due to inconsistent reporting to cancer registries. Efforts in recent years to improve MPN reporting may show more consistent incidence across Australia in future atlas updates. If not, reasons for such disparities in incidence will need to be closely examined.

Of even greater concern are the vastly different survival rates of MPN patients across the country. Hopefully this will be the subject of future research.

MPNs are listed as ‘classic MPNs’ in the atlas. You may wish to follow the visual explainers.  
It is available HERE.

Images below show the differences between MPN incidence and survival based on the latest available data from 2019.

The colour “ramp” visualises how the impact of cancer varies in a specific area compared to the Australian average. Blue means lower than average (or for survival, better), yellow represents the Australian average, and orange/red means higher than average (or for survival, worse).

Image 2:  MPN incidence across Australia in 2019

Image 3: MPN 5 year survival across Australia in 2019

 

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Optimal care pathways now available for MPNs

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The Leukaemia Foundation and Cancer Council have just released Optimal Care Pathways for Myeloproliferative Neoplasms.

Optimal Care Pathways (OCPs) are trusted guides that describe what optimal care for a particular type of cancer should look like. They put the patient at the centre of care decisions.

Covering every step from prevention and early detection through to recovery, living with a chronic disease, or end-of-life-care, they aim to improve patient outcomes through promoting quality cancer care and ensuring that all people diagnosed with cancer receive the best care, irrespective of where they live or receive cancer treatment.

Optimal Care Pathways can guide, support and inform increased collaboration, more effective care, improved healthcare provider–patient communication and patient experience. They have been signed off by state and territory governments.

Each OCP is made up of three documents:
1. The full OCP, a detailed and technical document outlining the pathways and timelines that define optimal care for someone diagnosed with this particular type of blood cancer (for healthcare professional use);
2. A short quick reference guide which summarises the OCP (for healthcare professional use); and
3. Your guide to best cancer care, a version of the OCP specifically designed for patients, carers and their families.

Who are Optimal Care Pathways for?
The OCPs are for healthcare professionals, patients, carers, and anyone affected by cancer or involved in cancer care.
The Leukaemia Foundation advises that OCPs should be read and understood by all healthcare professionals involved in cancer care – haematologists, oncologists, radiologists, surgeons, general practitioners, allied health professionals, nurses and cancer service managers, and trainees.

OCPs for MPN patients titled ‘Your guide to best cancer care’ are available in English for download HERE.
OCPs for MPN patients in several languages are available for download HERE.*
(*click on the grey shaded box that says PDF available for download in your language.)

OCPs for healthcare professionals are available for download HERE.

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MPN AA CALR research fellowship report

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Young myelofibrosis patient Sarah Gardner* raised a large sum of money for MPN research. Thanks to her brilliant fundraising, the MPN AA was able to fund a fellowship for Dr Chloe Thompson-Peach at the South Australian Health and Medical Research Institute.
The research focuses on the CALR mutation and it is extremely promising.

Australian CALR research

 

 

 

 

 

 

 

 

Image: Dr Chloe Thompson-Peach from SAHMRI

Chloe’s report from the fellowship follows.

Lay Report by Dr. Chloe Thompson-Peach, fellowship recipient

Myelofibrosis is an insidious condition of the bone marrow, which disrupts the normal production of blood cells. It is characterised by painful inflammation, low blood counts and fibrous tissue building up in the bone marrow. In some patients, myelofibrosis can also develop into acute leukaemia over time. The lack of effective therapeutic options for these cancers has led us to the development of a new immune treatment for these individuals.

We have developed a novel immune treatment, a biological therapy, that is a monoclonal antibody directed against the mutant CALR gene, which is the second most common cause of myelofibrosis or essential thrombocythemia.

We have shown this to be effective in cell lines and patient cells harbouring pathogenic CALR mutations in the laboratory.
Additionally, our treatment has also been shown to have no effect on cell lines and patient cells that do not carry mutations within the CALR gene, suggesting it is truly selective, which means it will not have side effects.

This was published recently in a major European science journal.

EXCITING UPDATE:

We have recently developed a new version of our antibody which is able to be used in humans without being rejected (called antibody humanisation) and demonstrated that the antibody is still effective at eliminating mutant CALR cells, while leaving healthy normal cells unharmed. We have shown that our antibody is able to significantly reduce the live burden of disease, with mutant cells being completely eradicated in pre-clinical in vivo experiments.

Our antibody reduced the number and size of megakaryocytes formed in CALR mutant patient samples in the lab, a key cell in driving myelofibrosis.

Additionally, we have shown that this antibody can be combined with Jakafi (ruxolitinib) to completely eradicate mutant CALR cells in the lab and re-sensitise cells that are resistant to ruxolitinib therapy alone.

Importantly, our human antibody has shown no signs of toxicity in mice and is in the process of preparation for clinical trial in the near future.

The good news is we have worked out which parts of the mutant CALR protein that causes myelofibrosis can be blocked by the antibody and it looks like we have another antibody that also has activity. We are now using the molecular information we have gained from these antibodies to build new cell therapies (CAR T cell or NK therapies or “bispecific T cell engager” antibodies).

We are hopeful that our research can build a suite of therapies, either to be used on their own or in combination with Jakafi, that will be effective and help move towards demonstration of long-term remission or cure in patients with myelofibrosis, as well as in patients that relapse after a stem cell transplant.

Some of our data was presented at the recent “New Directions in Leukaemia” conference organised by my supervisor Dr Dan Thomas at the University of Adelaide and Stanford University and is under review at a major international journal.

Please stay tuned and thank you for being committed to changing outcomes for patients with MPNs!

*Sarah Gardner’s story is available HERE.

 

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Important new study – high WCC as risk factor for blood clots in PV

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REVEAL study

Findings from an important new study for the management of polycythemia (PV) patients have just been released.

Called the REVEAL study*, it shows that leukocytosis (a high white cell count) is a risk factor for thrombosis (blood clots) in patients with PV. The study showed thrombosis to occur in high and low-risk patients, and even in patients in whom hematocrit was adequately controlled.

To date, known risk factors for thrombosis in PV patients included advanced age, previous history of blood clots, and elevated hematocrit >.45. There was insufficient data to include elevated white blood cell (WBC) counts as a known risk factor.

However, in an analysis of 2271 PV patients, the REVEAL study found 142 blood clots in 106 patients.
Specifically. during the study period of just under 4 years, it identified:

  • Significant associations with initial blood clot occurrence for hematocrit level >45% and WBCs >11 × 109/L .
  • Elevated WBC count was significantly associated with initial thrombosis in both low and high-risk PV patients.
  • Even when hematocrit was controlled at 45% or lower, WBC count >12 × 109/L was significantly associated with thrombosis.
  • There are different risk factors for arterial and venous thrombosis, an observation that has also been reported in essential thrombocythemia. Both leukocytosis and thrombocytosis (high platelet count), poor hematocrit control, and age were associated with a higher risk of arterial thrombosis, whereas female sex, history of previous thrombosis, and leukocytosis turned out to be the main risk factors for venous thrombosis.

The study’s authors feel that, even without a large study proving that lowering leukocytosis reduces blood clots, there is sufficient evidence to ‘support the inclusion of leukocytosis in the definition of high-risk polycythemia vera’. They also suggest that two elements of clinical practice could be changed:
– ‘low-risk patients with persistent leukocytosis could be elevated to the high-risk category and, therefore, be candidates for cytoreduction’ and
– ‘normalization of leukocytes should be included as an objective of treatment in patients receiving cytoreduction.’

There are two abstracts available discussing the REVEAL study’s findings.

REVEAL puts leukocytes into risk stratification 

Association between elevated white blood cell counts and thrombotic events in polycythemia vera: analysis from REVEAL

* REVEAL is a prospective observational study that enrolled 2510 patients with PV, with median follow-up of 44.7 months (range, 2-59 months). REVEAL stands for The Prospective Observational Study of Patients with Polycythemia Vera in US Clinical Practices.

 

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New WHO guideline for diagnosis of anaemia

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The World Health Organisation has just revised its guideline for diagnosis of anaemia thanks to a team of Australian researchers from the Walter and Eliza Hall Institute in Melbourne, led by Professor Sant-Rayn Pasricha.

These Australian researchers  have already:

Whilst this WHO guideline is for diagnosis of anaemia in general populations and does not refer to anaemia in the context of myeloproliferative neoplasms, we are excited to report on the contribution made to the field by Australian researchers.

The ABC’s ‘Health Report’ interviewed Professor Sant-Rayn Pasricha to explain the new guideline and how it was arrived at.
Listen to the interview  HERE.

The guideline is titled ‘Guideline on haemoglobin cutoffs to define anaemia in individuals and populations’ and is freely available to download in PDF form HERE.

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Webinar – Creating meaning in the face of blood cancer – now available

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The Leukaemia Foundation have added another webinar to their suite of general webinars which focus on living well.

The latest webinar is now available and is about creating meaning in the face of blood cancer.
It is available HERE.

And don’t forget the wonderful webinar from Dr Ranjana Srivastava. Dr Srivastava is an oncologist with a wealth of experience.
She has fantastic tips for coping with a cancer diagnosis, ageing and living with blood cancer and we highly recommend it.
The webinar featuring Dr Srivastava is available  HERE.

 

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More research showing anti-cancer benefits of exercise

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The Cancer Council, in conjunction with the Victorian government, has just released an informative study about the importance of exercise in reducing cancer risk. Their new research estimates that more than three times as many cancers are attributable to physical inactivity than previously thought.

The cancers that were linked to physical inactivity were: breast, colon, bladder, endometrial, kidney, oesophageal adenocarcinoma, gastric, non-Hodgkin lymphoma, head and neck, myeloma, myeloid leukaemia, liver, and gallbladder.

Associate Professor Brigid Lynch, senior author of the paper, said the findings provide a contemporary understanding of the cancer burden due to physical inactivity.
“We now know being physically active reduces the risk of 13 types of cancer. This new research highlights the number of individual cancer diagnoses that could have been prevented if Australians were better supported to integrate regular physical activity into their day.”

The news article also goes onto say that “Australia is a nation proud of its health system, yet we don’t have a physical activity plan or coordinated national physical activity strategy. Combined with changes in food supply, eating behaviours, a rise in convenience and ultra-processed foods, we are living in environments that do not promote healthy lifestyles.”

The news item from the Cancer Council can be accessed HERE.

 

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Unusual site thrombosis: literature review and insights

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Exploring the Molecular Aspects of Myeloproliferative Neoplasms Associated with Unusual Site Vein Thrombosis: Review of the Literature and Latest Insights

A paper has just been released about unusual thrombosis sites in patients with myeloproliferative neoplasms.
It includes a literature review and valuable insights into these occurrences.

The abstract explains that ‘MPNs are the leading causes of unusual site thrombosis, affecting nearly 40% of individuals with conditions like Budd–Chiari syndrome or portal vein thrombosis.’ The authors state that ‘a multidisciplinary strategy is vital to accurately determine the specific subtype of MPNs, recommend additional tests, and propose the most effective treatment plan. Establishing specialized care pathways for patients with splanchnic vein thrombosis and underlying MPNs is crucial to tailor management approaches that reduce the risk of hematological outcomes and hepatic complications.’

The full paper is available HERE.

 

 

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2024 guidelines on essential thrombocythemia

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These guidelines titled ‘Essential thrombocythemia: 2024 update on diagnosis, risk stratification, and management’ have just been released. They are a collaboration between the American haematologist Professor Tefferi and Italian haematologists Professor Vannucchi and Dr Barbui.

For a direct link to these comprehensive 2024 guidelines, see HERE.

We have also put a link onto our ‘MPN guidelines and articles‘ page.

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