Optimizing Treatment in Myeloproliferative Neoplasms - Episode 13

Patient Selection for Treatment of Polycythemia Vera

Transcript:Srdan Verstovsek, MD, PhD: Once we have a diagnosis of polycythemia vera, we assess the risk of blood clotting. The patients are usually divided in 2 groups. That would be patients with a low risk for thrombosis and high risk for thrombosis. If the patient has a high risk for thrombosis, then phlebotomy and aspirin are not good enough. For low-risk patients, phlebotomy and aspirin are standard practice. The goal of the phlebotomy usually is to reduce the hematocrit to less than 45%. That has been validated in a prospective randomized study, published in January of 2013, that clearly showed that patients with a strict control of hematocrit below 45 have advantage over those patients that do not have such strict control. I’m talking about decrease of cardiovascular events and even mortality related to those complications with the blood clotting and bleeding.

It’s very important to try to maintain and strictly maintain hematocrit below 45 with phlebotomy. Aspirin is added to maintain perhaps easier blood flow to decrease the thickness of the cells, but in the high-risk patients that have a high risk for thrombosis within the PV group, the phlebotomy is not good enough. So, we add hydroxyurea or interferon, which are the generally acceptable guidelines, to maintain the hematocrit all the time, if possible, as a level below 45% and further decrease the risk of blood clotting. Cytoreductive therapy is mandatory in patients that are older than 60 or have a history of blood clotting. Those are 2 factors that will identify patients with high risk. And, the goal of therapy traditionally has been hematocrit maintenance below 45%.

Kim-Hien T. Dao, DO, PhD: For patients with PV who are failing phlebotomy with hydroxyurea, we should consider other treatment options to control the hematocrit, and also symptoms in some cases. And I think for the younger patients, they can tolerate interferon quite well. So, this is a consideration for my younger patients. Usually, we’ve been going toward pegylated interferon because the toxicity profile is better than interferon.

In the older population, their intolerance to interferon is actually a little bit lower. And so, in these patients, you have to really carefully consider their comorbidities and also their side effects, and toxicities when considering interferon. For example, some patients may have autoimmune disorders or Parkinson’s disease, which may be conditions that you would be hesitant to use interferon. So, if the patients are not candidates for interferons for any of those reasons, then I do consider ruxolitinib, which has been FDA approved as second-line therapy for those patients that are hydroxyurea-intolerant or have failed hydroxyurea. I think ruxolitinib, according to the RESPONSE and RESPONSE-2 trials, has shown that it’s very efficacious and safe in providing hematocrit control, while also reducing spleen volume and also controlling symptoms associated with the polycythemia vera.

Daniel J. DeAngelo, MD, PhD: For patients with polycythemia vera—in addition to low-dose aspirin, hydroxyurea, and ruxolitinib—interferons have been utilized, both by themselves and in combination. They seem to be used mostly in younger patients or the rare incidence when you see a patient who’s pregnant and has a chronic myeloproliferative disorder. Other agents, such as histone deacetylase inhibitors, have been used in combination. Checkpoint inhibitors and other immunologic agents are beginning to be explored, but right now, those are in their infancy. And the mainstay in the therapy—in addition to phlebotomy, aspirin therapy—is hydroxyurea, interferon, and ruxolitinib.

Transcript Edited for Clarity