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BSH 2022 | Recent updates in the MPN field: clinical trials, novel agents, and more

In this video, Claire Harrison, MD, FRCP, FRCPath, Guy’s and St Thomas’ NHS Foundation Trust, London, UK, gives an overview of ongoing and future research in the field of myeloproliferative neoplasms (MPNs). Prof. Harrison first discusses updates in essential thrombocythemia (ET), including studies investigating the use of bomedemstat and pelabresib for the treatment of ET. Prof. Harrison then discusses updates in polycythemia vera (PV) and clinical trials in this area, including the MAJIC (PV) study and the MITHRIDATE study (NCT04116502). To conclude, Prof. Harrison discusses novel treatment combinations in myelofibrosis and ongoing trials in this field, including the MANIFEST-2 and TRANSFORM-1 studies. This interview took place at the 62nd Annual Scientific Meeting of the British Society for Haematology (BSH) 2022, in Manchester, UK.

Transcript (edited for clarity)

Well, the MPN field is currently a really busy field with lots and lots of new data, new agents, lots of clinical trials. So I think the important ones just now we’re evaluating two agents in essential thrombocythemia. One is bone bomedemstat, which is an LSD1 inhibitor. Very nice data presented at ASH with regard to controlling the platelet count and symptom burden, reducing as well as allele burden reduction, no data yet, but also some investigation with pelabresib, which is the BET inhibitors, CPI-0610, which is also being tested in ET...

Well, the MPN field is currently a really busy field with lots and lots of new data, new agents, lots of clinical trials. So I think the important ones just now we’re evaluating two agents in essential thrombocythemia. One is bone bomedemstat, which is an LSD1 inhibitor. Very nice data presented at ASH with regard to controlling the platelet count and symptom burden, reducing as well as allele burden reduction, no data yet, but also some investigation with pelabresib, which is the BET inhibitors, CPI-0610, which is also being tested in ET. So those are really important trials. It’s a long time since we had a new drug for ET. In polycythemia vera, there are trials currently underway looking at hepcidin mimetics and reducing the need for venesection. So for example, PTG-300, rusfertide, very interesting data. Also interesting that it, as well as reducing the need for phlebotomy appears to control iron deficiency-related symptoms, which can be difficult, like fatigue and pruritus et cetera.

I’m really happy that in the UK we’ve completed our analysis of the MAJIC-PV study and really look forward to presenting what are very, very exciting data hopefully later in the year. So hopefully we can have another conversation about that because I think it’s going to change the way we think about treatment of PV. And in a UK and French collaborative, we are doing an academic study called MITHRIDATE, where we’ll be looking at ruxolitinib upfront compared to interferon or hydroxyuria with a long follow-up and addressing some of the biological questions, is controlling the allele burden important, et cetera. And then finally thinking about trials, and when there are so many trials in myelofibrosis, trying to make first-line treatment better. So combining ruxolitinib with navitoclax, combining ruxolitinib with pelabresib, both of those are currently underway, MANIFEST-2 two TRANSFORM-1, and then similar agents in the second-line setting or other drugs.

So there are so many trials in myelofibrosis, but what I think is something to watch out for, for your viewers is actually the clinical translational work, which is helping us to try to move forward to identify surrogate endpoints, which are important beyond just reducing the spleen and controlling symptoms, which are clearly important for quality of life of patients. But what marks a patient who’s going to have a really good response and hopefully a survival benefit, and some things that are coming to the fore here are reduction of bone marrow fibrosis, reduced JAK allele or other variant allele frequencies. So these are the things that I think we should be looking at for this year.

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Disclosures

Research funding: Celgene, Constellation, Novartis
Advisory role: AbbVie, AOP, BMS, Celgene, CTI, Novartis, Galacteo, Geron, Gilead, Janssen, Keros, Promedior, Roche, Shire, Sierra

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