Video

Other Pathways Studied for MF

Transcript:Harry P. Erba, MD, PhD: Other pathways being targeted—BCL2, PI3 kinase? Is this the only pathway that we’re able to target in MF [myelofibrosis], or are there other ideas of how to move forward?

Ruben A. Mesa, MD, FACP: Fortunately, I think there has been a tremendous and justified interest in MPNs [myeloproliferative neoplasms] and myelofibrosis. Multiple things are being looked at in parallel, both alone and in combination. One I’d highlight would be PRM-151. This is an anti-fibrosing agent. It’s a recombinant human contraction 2 molecule, and its impact is really against the monocytes and macrophages. It impacts, really, the fibrosing process. The data have been seen in the early studies, both alone and in combination with ruxolitinib, in studies from Dr Srdan Verstovsek, me, and others. That is interesting, and it’s acting in a different pathway. We’ve seen activity with other pathways, including telomerase inhibition, in combination with PI3 kinase inhibitors. More than 1 PI3 kinase inhibitor has shown a preliminary activity. Rami, what about luspatercept?

Rami Komrokji, MD: That’s the other pathway, and I think the TGF beta pathway has also been a target. Within the consortium, we are starting a study in a different way, but 1 of the elements in that pathway had been those fusion trap proteins—luspatercept—that had finished clinical trials in MDS [myelodysplastic syndrome] showing efficacy in terms of anemia and had been tested in myelofibrosis. The study has actually finished accrual now.

A similar compound called sotatercept, also originally tested in MDS and myelofibrosis, had shown early activity in myelofibrosis. It was a small study with around 15 patients, but there were responses. I think the luspatercept may fill that unmet need of anemia for patients with myeloproliferative diseases. Hopefully, this study will tell us more about the efficacy and duration of responses. The whole pathway to the TGF beta pathways and other pathways has been actually looked at in different trials with different medications. There are drugs like luspatercept—again, that’s a fusion trap protein. There are tyrosine kinase inhibitors that target that pathway. We’re definitely going to see more trials in that way.

Jamile M. Shammo, MD, FASCP, FACP: Not to mention the combination studies. There’s a whole slew of combination trials—PI3 kinase delta, etc.

Transcript Edited for Clarity

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