Targeted Treatments for Myeloproliferative Neoplasms - Episode 5

Selecting and Sequencing Therapy in Patients With Polycythemia Vera


Considerations for the selection of optimal therapy in patients with polycythemia vera, and how these novel agents may be sequenced in the event of disease progression.


Pankit Vachhani, MD: Dr Komrojki, if you can tell us how you sequence the therapies. We talked about hydroxyurea®, interferon®, ruxolitinib®. How do you sequence the therapies for patients with PV? And while you are doing that, how do you monitor for adverse events? And those adverse events, which are the common ones, how do you prevent or manage when those occur?

Rami S. Komrojki, MD: Absolutely. You provide a nice view of the mechanism of action of those drugs, their activity. And obviously the decision always of the treatment and the sequence is based on benefit and risk analysis. As you mentioned earlier, the backbone for patients with P vera is always starting with phlebotomies as well as baby aspirin. And the goals are obviously on the short term, preventing thrombotic event, on the long term, maybe hopefully now altering the natural history of the disease in some patients. Always I get asked the question, are phlebotomies bad. Not necessarily, obviously they are not convenient for the patients, but if you are having frequent phlebotomies, that's indication of inadequate control of the disease. Most people set the goal of the response, controlling the blood counts, having a complete hematological response, no splenomegaly, no symptoms, but also lack of phlebotomies because it reflects that you're controlling the disease. Now with the NCCN guidelines, as I mentioned, even the low risky group could be candidates for interferon-based therapy. In general, in younger patients, lower risk patients, I would discuss ropeginterferon® now with the data and appeal that this could change the natural history of the disease. Obviously, those patients must be motivated. And the importance to understand that interferon takes a little bit longer time to work than hydrea® it takes 6 to 12 months to control the count. And it's a treatment that's going to be a long-term treatment. Patients need 2 to 3 years at least of the treatment to see the molecular benefit or response. But there is substantial evidence from interferon-based data, pegylated interferon and ropeginterferon®, that those medications could alter the natural history in a subset of patients. Obviously, they have their side effects, people that have used interferon in the past. The old format for melanoma or renal cell cancer are very aware of the adverse effects. The pegylated forms or the ropeg have less adverse effects, but obviously flu like symptoms, aches, fatigue can be sometimes prominent. The major ones to observe for, that there could be depression with this. Somebody with history of- background of severe depression or suicidal ideations should not be offered. Or people with mild depression should be observed very closely. It can cause some cytopenias, transaminitis. Those are the things we observe with interferon based therapy. My approach with the patients always saying, most of those adverse effects are reversible. Let's try it. If tolerance is reasonable, we can continue the treatment. Hydrea, obviously people have more experience with it. The major issue with Hydrea is cytopenia, particularly once we go up in the dosing to the range of 2 to 3 grams, we start seeing more adverse effects, not just the cytopenia, but mucositis. Most people with- define hydrea® resistance as having 2 or 3 grams of hydrea® not achieving the endpoints we discussed. Ruxolitinib® in general, again, is well tolerated. In terms of management or monitoring toxicity, we monitor the blood counts at the beginning. We see some count drop less in P vera than obviously in patients with myelofibrosis. Rarely some viral reactivation, headaches, bruising. But in general, and in P vera, the dosing of ruxolitinib® is very well tolerated. In general, obviously if patients are lower risk, young, motivated, I will discuss with them interferon. If they can't tolerate, then we'll go to the classical management. Older patients or higher risk patients. Again, if they can't tolerate interferon, that's a discussion, hydrea® for first line. For patients that, as you mentioned, have splenomegaly, constitution symptoms, that's where ruxolitinib® has a role. And we end sequencing those treatments based on what was the first choice, the tolerance. When we have a treatment failure, then we could go to the other options available.

Transcript edited for clarity.