The 2022 Tandem Meetings | Current and emerging management strategies in polycythemia vera
Srdan Verstovsek, MD, The University of Texas MD Anderson Cancer, Houston, TX, outlines current and emerging treatments for patients with polycythemia vera (PV). Today, most patients with PV are treated with phlebotomy, aspirin, and cytoreductive therapies, of which the most commonly used is hydroxyurea and more recently, ropeginterferon alfa-2b. Dr Verstovsek explains that adding rusfertide to cytoreductive therapy could eliminate the need for phlebotomy and normalize hematocrit levels, therefore reducing the risk of death. This strategy is going to be evaluated in a Phase III trial. This interview took place at the Transplantation & Cellular Therapy (TCT) Meetings of ASTCT™ and CIBMTR® 2022 in Salt Lake City, Utah.
Transcript (edited for clarity)
Polycythemia vera is a quite interesting disease. People have very high red blood cell count. Many have a high level of platelets. Many may have a circulatory symptoms from those high numbers of cells in the circulation, and some may have a big spleen. So standard practice is for,the majority of the patients to be treated with phlebotomy and aspirin, and a cytoreductive therapy to normalize those blood cell counts...
Polycythemia vera is a quite interesting disease. People have very high red blood cell count. Many have a high level of platelets. Many may have a circulatory symptoms from those high numbers of cells in the circulation, and some may have a big spleen. So standard practice is for,the majority of the patients to be treated with phlebotomy and aspirin, and a cytoreductive therapy to normalize those blood cell counts. Two-thirds of the patients are given what we call cytoreductive therapy. One third is just fine with the phlebotomy and aspirin alone. But in that setting, we have hydroxyurea, we have interferon and we have ruxolitinib or Jakavi as the cytoreductive therapies. And we usually, nine out of ten times, treat patients first with hydroxyurea. Those that don’t do well, 20% usually don’t, we then switch to ruxolitinib. And since November last year, we can actually, instead of any of these, utilize Besremi, which is commercial name ropeginterferon, which is now full fledge in NCCN guidelines, number one choice, along with hydroxyurea, as a therapy for people that need cytoreduction.
So we are in a very good shape, but the reality is that there is room for more. Those therapies work very well in a good proportion of the patients, but we can enhance what we do by adding medications that would possibly even eliminate completely. By adding it, for example, to cytoreductive therapy that I described, completely eliminate the need for phlebotomy, normalize the hematocrit below 45%. And that would subsequently decrease the risk of dying, because uncontrolled blood cell count leads to uncontrolled risk of blood clotting, and blood clotting is the main reason for dying. So adding, for example, investigation agent rusfertide, which is a hepcidin mimetic, you would allow better control of iron, less iron in the bone marrow, which is different than what you want in myelofibrosis. There is less iron in polycythemia vera patients in the bone marrow and no phlebotomy.
So there is a plan for Phase III randomized study based on extremely good results with rusfertide in a Phase II study. The Phase III study would be a randomizing patients with PV who have too many phlebotomies. Whether they’re on cytoreductive therapy or not, doesn’t really matter. Most of them as I described are, but they are not really responding very well. They have too many phlebotomies. They will be randomized between placebo and rusfertide, with the goal of eliminating phlebotomy. Which again, for me as a doctor means less of thrombotic risk and less risk of dying. So another new view on the how to approach therapy of PV, very exciting stuff.
Read more...
