Opinion
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Emerging Therapies for Patients with PV
In his final thoughts, Dr Gerds discusses emerging therapies for the treatment of PV.
Aaron Gerds, MD, MS: In polycythemia vera [PV], there’s a number of very exciting agents being developed. And it’s kind of a cool story, where I’m not sure too many other disease areas have this neat little story that we do here in MPNs [myeloproliferative neoplasms]. On the one hand, we’re targeting hepcidin and trying to reduce hepcidin to improve red cell production in myelofibrosis. On the flip side, we’re targeting hepcidin and pushing up the hepcidin levels to reduce red cell production in patients polycythemia vera. So we’re hitting the same pathway. Do we try to do opposite things for opposite diseases within our own category of disease, which is really kind of a fascinating story in [and] of itself. But in polycythemia vera, there are drugs like rusfertide…that aim to use hepcidin to trick the bone marrow into thinking it is iron deficient when it really isn’t…can replete [a patient’s] iron stores, but yet their bone marrow is not making red cells, I think is a very exciting option on the horizon for patients of mouth with polycythemia vera. [There are] other drugs like bomedemstat, which is an LSD1 inhibitor, [which] basically reprograms megacarrier sites, the cell of disease within the bone marrow space, to behave more normally. And we’re seeing clear responses in clinical trials, phase 2 trials that are ongoing with that agent. And there’s another drug called givinostat that’s in development [that] we’ll be launching in a phase 3 trial toward the end of the year. And that disease in phase 2 trials also has shown a significant disease modification. When we use the term disease modification in this instance, we’re talking about driving down the amount of disease in the bone marrow by however you want to measure it and really truly trying to change the disease course in a deep and meaningful way. There are certainly lots of other therapies being developed, so it is quite exciting to see these new treatments coming along for polycythemia vera [that] will hopefully be available soon for everyday use.
In the updated guidelines, we’ve changed some of the terminology just to bring it in line with the true sense of these diseases. A patient with polycythemia vera doesn’t necessarily need to go through myelofibrosis in order to have accelerated or blast phase disease. Blast phase disease, blast phase MPN, or blast phase PV, to be specific, is any instance where we see at least 20% blasts in the blood or bone marrow. That’s akin to acute myeloid leukemia [AML]. But we know that blast phase MPN is a much more aggressive disease than general garden variety, de novo AML. We really wanted to point that out. It’s not just AML, it’s its own beast and a very aggressive disease. So we want to avoid that at all costs. But the point being, though, for this change is [that] a patient’s disease does not have to pass through myelofibrosis in order to get to accelerated blast phase disease. It doesn’t have to pass through myelofibrosis. So we wanted to make that point clear, that if you start seeing high numbers of blasts in one’s blood or marrow, that it doesn’t necessarily mean that they’re in myelofibrosis. They could have progressed to accelerator blast disease, and that needs to be sorted out so the appropriate treatments can be applied going forward.
I think this modification of calling out accelerated of blast phase disease as opposed to just myelofibrosis that has transitioned to AML, I think kind of just puts more emphasis on the fact that, you know, the MPNs are a distinct group of diseases. They’re not AML; they’re their own thing, and we should think about them as such. And I think it draws awareness to the fact that these diseases can progress through various stages or [even] skip stages. If you think about it…it’s more of a matrix and not necessarily like a direct sequence. So when a patient’s disease does progress and [is] maybe progressing to accelerated or blast phase disease, [we should be] acting quickly to address it, because as those counts go up, those blast counts go up, the disease gets much, much harder to control. I think it brings awareness that this can happen and that we address it quickly with the appropriate therapies to get it back under control.
Transcript is AI-generated and edited for clarity and readability.
