Polycythemia Vera: PROUD-PV Trial

Harry P. Erba, MD, PhD: I completely agree with those comments about symptom control outside phlebotomy control, hematopoietic control, and splenic volume reduction. We now have more tools for treating patients, and we alluded to 1 earlier: pegylated form of interferon, and Ruben alluded to the updated EHA. Srdan, do you want to tell us about the PROUD-PV study?

Srdan Verstovsek, MD, PhD: We are talking about the major development in the polycythemia vera arena in terms of new therapeutic options. Perhaps many colleagues in the United States do not know that a year ago, there was approval of ropeginterferon, what I call a super long-acting interferon, in Europe for polycythemia vera patients. It’s given under the skin every 2 weeks, and after a year, you can even switch to once a month. It was approved to be given to patients with polycythemia vera for control of the blood cell counts.

The goal is complete hematopoietic response, not in patients with a big spleen, because it’s perhaps not applicable when given to patients with big spleens. In that setting, the drug has been superior, after about 3 or 4 years of therapy, to hydroxyurea. That was the PROUD-PV study that you mentioned: the randomized study between hydroxyurea and ropeginterferon in patients who were either newly diagnosed, not previously treated with cytoreductive therapy, or already on hydroxyurea for some time but not optimally managed.

They were not refractory and not resistant, but there was room for improvement. In that randomized study, the analysis showed that, after 1 year, there was no superiority of interferon, but we know that interferons take time to work. After several years, 3 or 4 years, superiority was seen.

Regardless of the comparison to hydroxyurea, the label allows its use for polycythemia vera, and it doesn’t talk about first- or second-line, or about it being superior or inferior to hydroxyurea, which is in accordance with the European leukemia guidance and the NCCN Guidelines as well. Ruben described this well: The guidelines would say cytoreductive therapy and hydroxyurea or interferon.

At least in Europe, and hopefully soon in the United States, we’ll have a ropeginterferon to offer to our patients. It is much less toxic, it has better efficacy when you have less toxicity, and I’m looking forward to embracing these in our own patients here at The University of Texas MD Anderson Cancer Center.

Harry P. Erba, MD, PhD: Before we move on, any other comments about what’s coming or what’s new in PV? That was the major highlight coming out of EHA. One final question about the use of interferon: It’s been touted as something that is more of a disease-modifying agent because some earlier studies show decreases in, for example, the JAK2 allelic burden. Has that been shown? Can you tell us about that from the PROUD-PV or other randomized trials, Srdan?

Srdan Verstovsek, MD, PhD: This particular information is quite interesting because this is the only therapy that may, in some patients, give an eliminated JAK2 clone by virtue of not being detected by our sensitive testing. That has been noted in the past with commercially available long-acting interferon Pegasys [peginterferon alfa-2a] in clinical studies.

This is offline use of that medication, but in ropeginterferon studies at the last ASH, there was a similar report of about 10% to 15% of the patients achieving the molecular response, not detectable JAK2 mutation anymore.

We hope that means a lot for these people, but perhaps it’s not a cure. We don’t associate this with a cure, but if you have no detectable JAK2 mutation, that would mean that there may be no or minimal malignancy there anymore. That would perhaps cancel it in the long-term benefit for these patients in the future. It is something to follow; it’s not the goal of the therapy, but it’s an interesting correlative study that is evidence of the biological ability of these medications to alter, possibly, the natural course of the disease.

Transcipt Edited for Clarity