Interferon's Role in Treating Polycythemia Vera


Harry P. Erba, MD, PhD: We’ve talked a lot about hydroxyurea and ruxolitinib, but interferon is still out there. Jamile, in which patients would you even consider interferon? Are there any data to support its use over hydroxyurea?

Jamile M. Shammo, MD, FASCP, FACP: I don’t consider interferon for people who are interested in having children, women or men of child-bearing age, obviously. The data on interferon come from 2 sources. There’s the MPN [myeloproliferative neoplasm] Research Consortium trial, and then there’s the PROUD-PV, which is a multicenter, randomized, phase III study looking at ropeginterferon, which is a mono-pegylated interferon, a cleaner version, essentially.

They randomized patients who had PV [polycythemia vera] to either the ropeginterferon or hydroxyurea. Now, they allowed patients who had PV who have been treated with up to 3 years of Hydrea. Those weren’t necessarily treatment-naïve, and the primary endpoint was to look at complete hematological response at 12 months. The definition of that was absence of splenomegaly, freedom from phlebotomy for at least 3 months, and normalization of the counts. Now, interestingly, at the 12-month mark, there was really no difference. This was a noninferiority trial, so there was no difference between the 2 agents.

The 24-month follow-up did seem to suggest that perhaps responses are a little bit more robust in the interferon, and particularly when it comes to molecular responses. I think the word is still out on whether it’s the compound itself as opposed to Pegasys, and we’ll hear more from Ruben about the next trial.

Harry P. Erba, MD, PhD: Ruben?

Ruben A. Mesa, MD, FACP: The second study is with the pegylated interferon alfa-2a developed by Roche and Genentech, so slightly different formulation than the ropeg [ropeginterferon], which Jamile had mentioned with the other study. This was through the MPN Research Consortium, of which Rami is a fellow member, and that is an NCI [National Cancer Institute]-supported P01 grant that supports this small, cooperative group doing these studies. Many of us, including Mary Frances and others, were involved with the development and the conduct of this study.

What this study demonstrated most clearly was that at a year, for high-risk patients, hydroxyurea and pegylated interferon were equivalent. There’s a subtlety between the 2 drugs in terms of adverse effects and response, but clearly, both were efficacious as frontline for helping to decrease that risk of thrombosis or bleeding. They clearly both had an impact on symptoms, although some very bitterly, including some toxicities that were a bit more on the interferon side, such as fatigue or flu-like symptoms, and some others on the hydroxyurea side.

Now, the study had limitations in terms of power, duration, and length of therapy due to a variety of implications in terms of access to the drug and other things. What we’re not able to answer is, at 5 years or 10 years, is interferon a better therapy? It may well be, in terms of a better, longer-term control of the disease over hydroxyurea. Although this study, by those limitations, isn’t able to answer that. I would say the discussion I have with patients currently is around that initial cytoreductive therapy. I think these 2 studies do support that interferon is a reasonable alternative for hydroxyurea as your frontline therapy—for younger patients, women of child-bearing potential, people at higher risk of skin cancers, and any number of things, but I think it’s a solid frontline consideration.

Harry P. Erba, MD, PhD: Before these trials, there were experiences, phase II studies, showing that you can actually have molecular response decrease in the JAK2 allele burden. Mary Frances, is this something important? Should we be monitoring JAK2 allele burdens with interferon or ruxolitinib, and has it translated into any important endpoints?

Mary Frances McMullin, MD, FRCP, FRCPath: Not yet. I don’t think we know whether it’s important. Then you get to JAK2 mutation, the primary event, and that’s another full discussion, but certainly in the French interferon trials, some of them had major decreases in the JAK2 burden. PROUD-PV starts to show a small decrease in the JAK2 burden. Then, some of the French patients were able to come off treatment, although it was a phase II, yet there was no control group. That may be important, but we really don’t know. Again, conceptually, if you’re thinking what you want to do to cure the disease, getting rid of the mutant clone would make sense. Most laboratories don’t have enough for routine monitoring yet, and I don’t think you’re going to change treatment on the basis of the allele burden, but I think that may be where we want to go in the future.

Harry P. Erba, MD, PhD: Outside of a research setting, it doesn’t sound like anyone monitors this for guiding therapy or recommends it.

Ruben A. Mesa, MD, FACP: We continue to look for the equivalent of a BCR-ABL—type monitoring level. Unfortunately, I don’t think JAK2 V617F is it.

Harry P. Erba, MD, PhD: OK.

Rami Komrokji, MD: Other mutations can sometimes be helpful. The presence of other mutations, whether it’s in terms of disease risk assessment, or sometimes predicting therapy. For example, with interferon, I think there are some data suggesting, for example, if patients have an IDH1 or IDH2 mutation, they may not benefit from the treatment. As mentioned, I don’t think we monitor this on a regular basis in the clinic.

Transcript Edited for Clarity

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