patient care perspectives

Management of Toxicities in Patients Being Treated for Polycythemia Vera

by Ruben A. Mesa, MD, FACP

Overview

First-line hydroxyurea is a therapeutic mainstay for cytoreduction in patients with polycythemia vera (PV); however, not all individuals with PV meet the treatment goals at the tolerated doses. Hydroxyurea is associated with hematologic and nonhematologic toxicities that may require a switch to a second-line cytoreductive agent.

Expert Commentary

Ruben A. Mesa, MD, FACP

Director, Mays Cancer Center at UT Health San Antonio MD Anderson
Mays Family Foundation Distinguished University Presidential Chair
San Antonio, TX

“Other patients on hydroxyurea may achieve the target hematocrit level, but their platelet counts are too high and they are neutropenic. It then becomes like robbing Peter to pay Paul. 

Ruben A. Mesa, MD, FACP

Dose-limiting toxicity with hydroxyurea is certainly a problem for some patients with PV. For example, some individuals may have neutropenia (with or without adequate control of the hematocrit or platelet count) at the hydroxyurea doses that they are able to tolerate. The  worst-case scenario involves the patient who is slightly neutropenic, but with platelet counts that are still too high and who still requires phlebotomy to control their hematocrit level. Other patients on hydroxyurea may achieve the target hematocrit level, but their platelet counts are too high and they are neutropenic. It then becomes like robbing Peter to pay Paul. 

Some retrospective studies have reported an association between hydroxyurea resistance or intolerance and an increased risk of transformation to primary myelofibrosis or acute myeloid leukemia. The magnitude of the leukemogenic potential of hydroxyurea in PV is controversial and it is difficult to study. If there is an effect, I do not believe that it is a dramatic one, but I do tell my patients with PV that there is sufficient evidence for concern regarding the long-term safety of hydroxyurea. Without question, hydroxyurea use is clearly linked to the development of cutaneous lesions, such as leg ulcers. There have also been reports of skin carcinomas with prolonged hydroxyurea treatment. 

There is limited evidence regarding the leukemogenic potential of second-line therapies for PV. Pegylated interferon may cause autoimmune disorders, mood disorders such as depression, and elevated hepatic enzyme levels. Busulfan, which is not commonly used for PV, may cause severe cytopenia and is likely more leukemogenic than other second-line therapies. Ruxolitinib may be associated with a slightly increased risk of shingles and nonmelanoma skin cancers; however, it is challenging to single out the adverse effects of this agent because most patients on ruxolitinib were previously treated with hydroxyurea, sometimes for long periods.

References

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.

Barosi G, Birgegard G, Finazzi G, et al. Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference. Blood. 2009;113(20):4829-4833.

Gerds AT, Dao KH. Polycythemia vera management and challenges in the community health setting. Oncology. 2017;92(4):179-189.

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