Myelofibrosis drug Momelotinib approved by the US FDA

Here is an Australian news item about the US FDA approval of Momelotinib, a new drug for Myelofibrosis. This is significant as there are few treatment options for those with myelofibrosis, and this is another option for those for whom other therapies are unsuitable. We would love to see it made available to Australian patients in the future.



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Polycythemia vera: 2024 update on diagnosis, risk-stratification and management

MPN specialist haematologists, the USA’s Ayalew Tefferi and Italy’s Tiziano Barbui have just released a very extensive overview of polycythemia vera.

The overview is detailed and includes:

  • an important update that recognises interferon as a first line treatment option along with hydroxyurea, as well as much discussion of the latest research into treatment options,
  • advice on pregnancy management in PV patients,
  • a detailed explanation of the genetic landscape and potential implications,
  • discussion of research on life expectancy,
  • and much more.

The article appears in the American Journal of Hematology and is open sourced and can be accessed HERE.

If you’d like to see more articles on polycythemia vera, our guidelines page can be accessed HERE.



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MPN experts: Roundtable series on PV

MPN specialists  Professor Claire Harrison, Guy’s and St Thomas’ NHS Foundation Trust from the UK, Professor Jean-Jacques Kiladjian, Saint Louis Hospital, Paris,  and Alessandro Rambaldi, MD, University of Milan have collaborated to provide an up to the minute roundtable series on management of polycythemia vera (PV). (Courtesy of the Oncology Learning Network).
Each video includes an accompanying transcript.

Part 1: Hematocrit control and cardiovascular assessment – HERE

Part 2: Aims of treatment and choice of appropriate first-line therapyHERE.

Part 3: Identifying when first-line therapy for PV might be failingHERE

Part 4: Second-line therapy and reviewing data on RuxolitinibHERE




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PV – hematocrit control and cardiovascular assessment

A recent presentation from MPN specialists Professor Jean-Jacques Kiladjian, Saint Louis Hospital, Paris, and Professor Claire Harrison, Guy’s and St Thomas’ NHS Foundation Trust from the UK discusses the importance of maintaining hematocrit control in patients with polycythemia vera (PV) as well as monitoring cardio-vascular health.

The discussion, part 1 of an expert roundtable series, is wide ranging and covers the risk factors for patients with polycythemia vera.
Of particular interest is the manner in which cardiovascular health is treated by Professor Kiladjian’s team in Paris.

Claire Harrison: “Jean-Jacques, we’ve recently been looking across some PV patients and thinking about how do we do cardiovascular risk stratification and assessment. I found out that we do this in a slightly different way, and I think you do it in the best way, so tell us how you do that in Hospital Saint-Louis.”

Jean-Jacques Kiladjian: “I’m not sure it’s better, but, yeah, it’s different. Well, we have a quite aggressive and proactive attitude regarding cardiovascular assessment of all patients with PV regardless of age. Obviously the older they are, they’re usually already followed by a cardiologist sometimes or they already had some cardiovascular events.

But even in younger patients with absolutely no history of cardiovascular events, we frequently refer them to a cardiologist, not any cardiologist, but a cardiologist that knows what we are looking for, that these patients are at high risk of cardiovascular problems in the future, that they will be followed for decades and we need this proper assessment.

At least an echocardiogram, doppler of arteries, peripheral arteries, is performed. We ask to perform that for almost every patient at baseline and then regularly every 2 to 3 years in patients without any risk factors, more frequently if needed. So yes, we have a quite very proactive attitude against these additional factors because we also noticed that—and maybe this is a field for the future as Alessandro said—that it’s not exactly maybe the same risk factors for arterial versus venous thrombotic events.

Maybe some characteristics of the disease, of the patients, may predispose more to arterial events that are more dangerous for the patients like myocardial infarction, stroke, et cetera, and these risk factors may be different. And the cardiovascular, let’s say landscape of the patient at baseline is very important to avoid and to prevent these arterial events.”

The full presentation with transcript is available HERE.

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Iron link offers new treatment hope for incurable blood cancer

Read more about the newly published findings on an iron link which offers a new treatment hope for polycythaemia vera.

“A landmark discovery linking iron regulation to a rare blood cancer has led to clinical trials of a potential new treatment for patients with the incurable disease.

The study focused on polycythemia vera (PV), a blood disorder causing excessive red blood cells, and found that restricting iron access to the bone marrow could reduce the production of red blood cells in this disease.

The research, led by WEHI (the Walter and Eliza Hall Institute of Medical Research) in collaboration with the University of Melbourne, the Peter MacCallum Cancer Centre, the University of Cambridge and Silence Therapeutics (UK), has led to new clinical trials of a drug that has the potential to control iron regulation in patients with PV.”

A link to the WEHI news release is HERE.

The Blood journal article referred to in the above news article is HERE.



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New treatment hope for PV


Dr Cavan Bennett (R) is pictured in the lab with Nathalie Cook OAM  (a PV patient) from the MPN AA who is part of the WEHI patient consumer program

A ground-breaking new treatment for polycythaemia vera (PV) has been developed here in Melbourne by researchers Dr Cavan Bennett and Professor Sant-Rayn Pasricha from the Walter and Eliza Hall Institute (WEHI). This treatment appears to avoid the need for venesections. Phase 1 clinical trials begin shortly. There will be 7 trial sites in Australia and more detailed information will be provided shortly.

A report on ABC Radio’s Health Report of 3 April this year outlines the potential benefits of this treatment for patients. The report is available to listen to HERE.

More detailed information about the research is available below.

” SLN124: ironing out a new treatment for Polycythaemia Vera (PV)

The average adult has approximately 3-4 grams of iron stored in their body. Large changes in the amount of stored iron can have drastic consequences, with too little iron (iron deficiency) causing chronic fatigue and brain fog. Two-thirds of the iron in the body is contained within red blood cells. As such, venesection (blood withdrawal – the first-line treatment of Polycythaemia Vera) induces iron deficiency by removing iron-containing red blood cells from the body. Consequently, chronic fatigue and brain fog are not uncommon in venesected patients.

A small amount of iron travels around the body in the liquid compartment of the blood (the plasma). Plasma iron supplies the body’s cells with their iron needs, most notably for producing new red blood cells. Iron in the plasma comes from two main sources: dietary iron and recycling iron contained within dying red blood cells in the spleen. The amount of iron entering the plasma is controlled by the levels of a hormone called hepcidin. Hepcidin prevents iron exiting the cells of the intestine and spleen and entering the plasma. Therefore, increases in hepcidin result in less plasma iron and, as such, less iron is available for producing new red blood cells. Hepcidin is produced in the liver and the biological pathway that leads to hepcidin production has an internal brake, which limits hepcidin production.

Researchers Dr Cavan Bennett and Professor Sant-Rayn Pasricha from the WEHI (Melbourne, Australia) therapeutically silenced hepcidin’s internal brake, TMPRSS6, in a new clinically relevant mouse model of Polycythaemia Vera. In doing so, they discovered that hepcidin levels increased and plasma iron levels went down. Furthermore, they showed that the increase in hepcidin acted as a sort of medical venesection and reduced the haematocrit of the Polycythaemia Vera mice by nearly 20%. However, they have revealed that unlike traditional venesection, therapeutically increasing hepcidin levels did not physically remove iron from the body and therefore did not lower the total body iron levels. Because of this, it is thought that compounds that silence hepcidin’s TMPRSS6 could replace traditional venesection. This would offer an alternative to venesection and importantly offer hope to the population of Polycythaemia Vera patients intolerant to venesection who currently have no alternative therapeutic options.

Dr Bennett and Professor Pasricha used a short interfering (si) RNA developed by Silence Therapeutics Plc to silence hepcidin’s TMPRSS6. SLN124 is a siRNA in development by Silence Therapeutics as a treatment for haematological conditions. SLN124 has a potential to modulate hepcidin by ‘silencing’ TMPRSS6 to increase hepcidin levels to restrict iron in the bone marrow thereby reducing red blood cell production. SLN124 is expected to replace venesection and reduce thrombotic risk while reallocating iron away from the bone marrow to improve PV symptoms including fatigue. SLN124 has demonstrated safety in healthy volunteers and is currently being assessed in patients with thalassaemia. A new study for SLN124 is starting in Australia (and other locations) to investigate the safety and efficacy of SLN124 in patients with Polycythaemia Vera. This is a two-part study:  the first part will look at different doses and the second part will compare a single dose with placebo. All patients participating in the phase 1 are eligible to participate in the phase 2. ”

The photo above was provided with kind permission of WEHI, and is Copyright:© WEHI (Walter and Eliza Hall Institute of Medical Research) 1G Royal Parade Parkville 3052


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Diagnosis and treatment of ET and MF in real life: 960 MPN patients in Germany

A fascinating study has just been released about diagnosis and treatment of patients with ET and MF in Germany, especially as a precise diagnosis impacts on access to approved therapies.

“This study reports on a chart review conducted to evaluate the real life approach regarding clinical characteristics, diagnostic assessment, risk stratification and treatment decisions for MPN patients classified as ET or MF after implementation of the WHO 2016 classification.”

“Of note, the proportion of JAK2 mutated patients was significantly higher in this selected cohort compared to published molecular studies. The presence of JAK2 driver mutations is associated with higher systemic inflammation, thromboembolic risk and disease progression.”

“Classification of MPN subtypes is not only critical to inform patients about risk of disease progression and probability of survival but also regarding access to approved pharmacologic therapies.
As shown in this chart review, more than 10% of patients classified as ET or MF report on significant symptom burden and may benefit from JAK-inhibitor treatment, approved for the treatment of disease-related splenomegaly or symptoms in adult patients with myelofibrosis. Conversely, the need for cytoreductive therapies to achieve TE risk reduction has been perceived and cytoreductive treatment had been initiated according to guideline recommendations (mainly using hydroxycarbamide/hydroxyurea).
This is of major importance considering the large number of patients in this chart review showing clinical and histopathologic findings consistent with pre-fibrotic myelofibrosis.”

Improved histopathologic diagnostics, dynamic risk stratification including genetic risk factors for cases of suspected ET and MF are recommended for precise risk assessment and therapeutic stratification according to WHO criteria.”

The full article titled ‘Diagnosis and treatment of MPN in real life: exploratory and retrospective chart review including 960 MPN patients diagnosed with ET or MF in Germany’ is available HERE.

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Myeloproliferative neoplasms and splanchnic vein thrombosis: Contemporary diagnostic and therapeutic strategies

A recent review from MPN specialist Professor Jean-Jacques Kiladjian in France and colleague Bruno Cassinat about current diagnostic and treatment approaches to splanchnic vein thrombosis is of interest.

The abstract recommends: “Therefore, though screening for JAK2V617F mutation should be the starting point of the diagnostic workup performed in all patients with splanchnic vein thrombosis, a multidisciplinary approach is needed to accurately diagnose the subtype of myeloproliferative neoplasm, recommend the useful additional tests (bone marrow biopsy, search for an additional mutation using targeted next-generation sequencing), and suggest the best treatment strategy. Indeed, providing a specific expert care pathway for patients with splanchnic vein thrombosis and underlying myeloproliferative neoplasm is crucial to determine the optimal management to reduce the risk of both hematological and hepatic complications.”

The full article is available HERE.

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Myelofibrosis patients with anaemia – published results from MOMENTUM trial

The Lancet has just published findings from phase 3 of the trial for symptomatic myelofibrosis patients with anaemia.

The trial was titled MOMENTUM and is officially referred to as “Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): results from an international, double-blind, randomised, controlled, phase 3 study”

Interpretation of the trial results is that “Treatment with momelotinib, compared with danazol, resulted in clinically significant improvements in myelofibrosis-associated symptoms, anaemia measures, and spleen response, with favourable safety. These findings support the future use of momelotinib as an effective treatment in patients with myelofibrosis, especially in those with anaemia.”

Due to the paywall, it is not possible to provide the full study. but the summary is available HERE.

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Real-world treatments and thrombotic events in polycythemia vera patients in the USA

A retrospective observational study of over 28,000 polycythemia vera (PV) patients in the USA has just been published in the January 2023 edition of the Annals of Hematology.

The main finding suggests that in the US, currently available PV treatments may not be used to full advantage.
Conclusions recommend “more detailed exploration in other studies, but these data do indicate substantial collective reliance on an established therapy, phlebotomy, despite a low percentage of patients achieving guideline-recommended results in hematocrit control, and 8% of low-risk and 20% of high-risk patients experiencing thrombotic events despite access to all available treatment options.”

The full article is available HERE.

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