New treatment hope for PV

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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

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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

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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

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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

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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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Video available – forum on menopause, HRT and MPNs

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An online forum was recently held in the UK focusing on ‘Menopause, hormone replacement therapy and myeloproliferative neoplasms.’
The panel included Debra Holloway, Nurse Consultant Gynaecology, Guy’s & St Thomas’ NHS Foundation Trust, Professor Claire Harrison, who is an MPN expert haematologist, and Advanced Nurse Practitioner Claire Woodley also from Guys & St Thomas’ hospital.

This video is available with thanks to the UK’s MPN Voice which provides wonderful information to MPN patients in the UK and more broadly.

PLEASE NOTE: There were some technical issues with the sound quality during a very small part of the video.

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MPN Horizons conference 2022

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Reflections on the 2022 MPN Horizons meeting, Netanya, Israel
from Ken Young, MPN AA team member

The MPN Horizons meeting was held this year in Israel and online.

It was a great success with many excellent presentations.
Ken recommends in particular watch the sessions from Medical Session 3 which feature Dr Gabby Hobbs, the MPN AA’s Nathalie Cook OAM and Dr Ruben Mesa.

Here is the link to the videos from MPN Horizons Hybrid Conference 2022

Ken Young watches on whilst Nathalie Cook presents at the November 2022 MPN Horizons Conference in Netanya, Israel.

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ASH 2022 summary of highlights

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Dr Ruben Mesa, an international MPN expert provides a summary of the highlights for MPN patients from the December 2022 American Society of Hematology (ASH) annual meeting.

CALR monoclonal antibody discovered!
Of particular note is the incredibly exciting news of the discovery of a CALR monoclonal antibody which has proven very successful in the laboratory. The CALR mutation is responsible for roughly 30% of ET and MF cases.
Patient clinical trials are expected to commence in the upcoming year. A measure of the importance of this breakthrough is that the research was featured in a plenary session at the conference.
Here is a link to a video from Ann Mullaly, MPN specialist and scientist from the US,  explaining in more detail how the CALR mutation is being targeted. (courtesy of MPN Hub).

Secondly, the video below from Ruben Mesa provides an overview of this and other promising developments from ASH.
Anne Brazeau, the founder and CEO of MPN Education and Advocacy International has kindly made available this video to the MPNAA.

 

 

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Interferons in MPNs: a conversation with an MPN specialist

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Anne Brazeau, the founder and CEO of MPN Education and Advocacy International has kindly made available an excellent wide ranging video about interferon use in MPNs.

  • The video showcases a presentation about interferons by Gabby Hobbs, MPN specialist and Clinical Director of Leukemia Service at Massachusetts General Hospital as well as being an Assistant Professor at Harvard Medical School.
  • Dr Hobbs discusses issues that haematologists take into account when considering interferon use in pregnancy. (35 minutes into the video).
  • Dr Hobbs also responds to a range of questions from MPN patients about interferon.

Note that while the video refers often to Besremi which is a longer acting pegylated interferon available in the USA, Europe, and some other countries, Pegasys is also a long acting interferon and Australians are extremely fortunate that it is available on Australia’s Pharmaceutical Benefits Scheme (PBS).

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Leukaemia Foundation – survey of blood cancer in Australia 2022

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The Leukaemia Foundation launched the National Strategic Action Plan for Blood Cancer in 2020. Its overarching principle is that ‘every Australian with a blood cancer should have equitable access to the best information, treatment and care wherever they live and whatever their background.’

As part of this plan, the Leukaemia Foundation is working towards a goal of zero lives lost to blood cancer by 2035.

To help get there, they need your knowledge and around 20 minutes of your time, to complete this survey.

All responses are anonymous.

Click HERE to begin the survey and be a part of change for the better to help people living with a blood cancer.

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