clinical topic updates
Treatment Recommendations for Durable Count Control in Polycythemia Vera
Durable count control in patients with polycythemia vera (PV) involves achieving a delicate balance between hematocrit, platelet, and leukocyte counts, and it necessitates long-term treatment tolerability. Successful management strategies may involve combinations of phlebotomy, low-dose aspirin, and cytoreduction with hydroxyurea or second-line agents such as ruxolitinib.
Director, Mays Cancer Center at UT Health San Antonio MD Anderson
“Durable count control also implies treatment tolerability, as PV treatment continues indefinitely. To achieve a durable therapeutic response, which correlates with long-term prevention of thrombotic complications in those with PV, the treatment must be tolerable.”
Maintaining durable count control in patients with PV is really about achieving control of the erythroid, thrombocytic, and myeloid cell lineages. Many individuals never attain adequate control of any lineage, or they attain control of 1 lineage but not another. For example, it is not uncommon to encounter patients with PV with controlled hematocrit levels but whose platelets are too high and neutrophils are too low. Or perhaps they have achieved control of 1 lineage but have toxicity in another. To me, achieving durable count control means getting all 3 sets of counts in the optimal range (ie, not too high and not too low).
Durable count control also implies treatment tolerability, as PV treatment continues indefinitely. To achieve a durable therapeutic response, which correlates with the long-term prevention of thrombotic complications in those with PV, the treatment must be tolerable. PV is characterized by clinical plateaus and periods of progression; however, the cell counts do not usually increase to the extent that they drive the need for frequent adjustments to cytoreductive therapy. Unfortunately, I have seen patients who have been managed on the maximum tolerated dose of hydroxyurea, whether or not they had achieved target levels of cytoreduction in all lineages. While the importance of hematocrit levels as a target is generally appreciated, I think that there is an inadequate recognition of the importance of leukocyte and platelet counts in determining the response to PV treatment. Count durability also flows from how well the therapy is tolerated. Patients who are receiving the right medication at the right dose can often continue on autopilot for long periods of time. They still need to be monitored, but they can remain on a remarkably stable regimen for a decade—or even longer—if the cell lineages are in balance. The combination of phlebotomy and aspirin is frequently inadequate for achieving durable count control. In fact, patients with elevated leukocyte or platelet counts have no chance of improving with phlebotomy and aspirin alone. The addition of cytoreductive therapy is beneficial in achieving durable count control, but it is too often delayed in patients with PV. And, once added, the cytoreductive therapy must be sufficiently benign so that the patient can take it continuously over a period of years without difficulty. Second-line agents such as ruxolitinib should be considered in cases of hydroxyurea intolerance, when there are uncontrolled symptoms such as splenomegaly, and, importantly, when count control is suboptimal.
Barosi G, Birgegard G, Finazzi G, et al. A unified definition of clinical resistance and intolerance to hydroxycarbamide in polycythaemia vera and primary myelofibrosis: results of a European LeukemiaNet (ELN) consensus process. Br J Haematol. 2010;148(6):961-963.
Gerds AT, Dao KH. Polycythemia vera management and challenges in the community health setting. Oncology. 2017;92(4):179-189.
Parasuraman S, DiBonaventura M, Reith K, Naim A, Concialdi K, Sarlis NJ. Patterns of hydroxyurea use and clinical outcomes among patients with polycythemia vera in real-world clinical practice: a chart review. Exp Hematol Oncol. 2016;5:3.
Rumi E, Cazzola M. Diagnosis, risk stratification, and response evaluation in classical myeloproliferative neoplasms. Blood. 2017;129(6):680-692.