Primary Myelofibrosis: Trials of Interest

Transcript:

Harry P. Erba, MD, PhD: Moving along from there, Srdan, we may soon have a third JAK inhibitor: pacritinib. Can you tell us about the data supporting that and how it would impact treatment options?

Srdan Verstovsek, MD, PhD: You are correct. There are other JAK inhibitors; there have been many JAK inhibitors in testing. Pacritinib is the 1 that is less myelosuppressive, and it can possibly be beneficial to patients who have lower platelets.

The thing with treating patients with lower platelets, and particularly platelets below 50,000 per mm3, for which fedratinib or ruxolitinib are not suggested, is that it is a hot topic: 10% to 20% of patients may have or develop low platelets over time, and there is nothing to do. The low platelet number is a bad prognostic factor.

In this setting, pacritinib is being tested at the moment in a randomized study, which is the 1 you mentioned, the PACIFICA study, specifically focusing on this group of people. It is an area of unmet need where the therapy with this drug may improve the symptoms and signs, and it may provide some durability of a good quality of life for unfortunate people like that. We are embracing that study very much. There is absolutely nothing else that can be done; there are no other studies in this setting at all.

Harry P. Erba, MD, PhD: Thank you. Ruben, how about a high-level view of what might be exciting at ASCO 2020 [American Society of Clinical Oncology Annual Meeting] or EHA [European Hematology Association Congress] in myelofibrosis [MF], not in PV [polycythemia vera].

Ruben A. Mesa, MD, FACP: Sure, there are a couple of things. First, pivoting off the pacritinib study, which I’m very excited about as a coinvestigator, I would highlight the momelotinib phase 3 study. Momelotinib is another JAK1/2 inhibitor with potential differentiation around anemia.

The MOMENTUM study is now going to be opening looking at patients who have difficult to control MF, who have failed ruxolitinib and have anemia. It’s a randomized study of momelotinib versus danazol. We’re going to be sharing at EHA some further updates regarding the mechanism of action of that agent, looking at suppressing hepcidin, which could be a mechanism in terms of improving anemia.

At this year’s ASCO, there was an interesting potential new therapeutic target that was mentioned regarding the use of CD47. It was a study that came out of the United Kingdom looking at CD47 on the cell surface as a potential target that might be applicable in both MPN [myeloproliferative neoplasm] patients and MDS [myelodysplastic syndrome] patients.

At EHA, we’ll also hear further updates in terms of important studies, in terms of both information from fedratinib as well as further updates from the BET inhibitor from Constellation Pharmaceuticals, Inc, that’s being looked at alone or in combination for more difficult MF, as well as other exciting updates from some of our ongoing studies.

Harry P. Erba, MD, PhD: Some of the most interesting biology that I’ve read about in the last couple of years is how the truncated calreticulin [CALR] protein is excreted from cells and acts as an agonist for the MPL receptor. I hope I didn’t tune out for a second there, but did you talk about targeting that CALR protein?

Ruben A. Mesa, MD, FACP: That is certainly held as an area of opportunity, and there are studies in development looking at both vaccine approaches and other cellular surface antibodies and such. None of those have reported any data yet, but it has been felt that calreticulin may be 1 of the more accessible targets in terms of the driver mutations because you can get to the cell surface.

That is certainly a hope: that we will be able to have that selectivity against the mutant-driving cells in those patients with MPNs. That would probably start with calreticulin-mutated patients with myelofibrosis who have more difficult disease.

Transcript Edited for Clarity

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