Management of polycythemia vera in the community oncology setting
Patients with the chronic myeloproliferative neoplasm polycythemia vera have shortened survival and often experience disease-related symptoms that negatively affect quality of life. Consequently, there is a demonstrable need for early diagnosis of polycythemia vera, followed by long-term, responsive, evidence-based disease management. The diagnostic and management landscape for polycythemia vera continues to improve, but gaps remain in diagnostic and treatment strategies. The diagnosis of polycythemia vera is based on World Health Organization criteria, and treatment goals for the condition include modifying the risk of cardiovascular and hemorrhagic events, reducing the risk of fibrotic and/or leukemic disease transformation, and alleviating polycythemia vera–related symptoms. The current treatment strategy for polycythemia vera is for all patients to receive aspirin and phlebotomy, with a hematocrit goal of <45%. Some patients may also benefit from cytoreductive therapy, typically with hydroxyurea. For those patients who become resistant to or intolerant of hydroxyurea, ruxolitinib is currently the only approved treatment option. This review provides community-based oncologists and other clinicians with an overview of current diagnostic and management strategies for polycythemia vera.
Accepted for publication April 28, 2017
Correspondence Michael R Grunwald, MD;
michael.grunwald@carolinashealthcare.org
Disclosures Dr Grunwald has served as a consultant, participated in advisory boards, and received research funding from Incyte Corp, the maker of ruxolitinib, a treatment option for polycythemia vera. Dr Scola has served on a speakers bureau for and is a stockholder of Incyte Corp. Dr Miller has served on advisory boards and speakers bureaus for, and received institutional research funding from, Incyte Corp and Novartis. Dr Onitilo has no conflicts to disclose. The authors received writing assistance from Complete Healthcare Communications, LLC, which was funded by Incyte Corp.
Citation JCSO 2017;15(4):e195-e203
©2017 Frontline Medical Communications
doi https://doi.org/10.12788/jcso.0349
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Possible future treatment options
Other possible treatment options for patients with polycythemia vera that are currently in clinical development include three pegylated IFN-α (PEG-IFN-α) variants and the telomerase inhibitor, imetelstat.
Pegylated interferon-α. PEG–IFN-α has the advantage of a longer plasma half-life compared with conventional IFN-α, permitting administration once per week or less often.46 Currently, three variants are under active investigation in phase 3 clinical trials: PEG–IFN-α2a (NCT01259856 and NCT01387763), PEG–IFN-α2b (NCT01387763), and AOP2014/P1101 (NCT02218047, NCT02523638, and NCT01949805).
Imetelstat. The telomerase inhibitor imetelstat is in clinical development for patients with MPNs. Clinical benefit was previously observed in patients with primary MF as well as post-polycythemia vera and post-ET MF.52 Imetelstat was evaluated in a phase 2 trial in patients with polycythemia vera or ET who required cytoreductive therapy and were resistant to or intolerant of ≥1 previous line of therapy or who refused standard therapy (NCT01243073). Results in patients with ET were published,53 however, findings from the polycythemia vera cohort have not been reported.
Community oncologist role in managing disease burden
Most patients with polycythemia vera are managed in the community setting. Consequently, the community oncologist plays a critical role in the initial diagnosis, risk stratification, patient education, and disease management.
Early disease recognition allows prompt therapeutic intervention with low-dose aspirin and phlebotomy, interventions shown to reduce the risk of cardiovascular events based on the ECLAP32 and CYTO-PV trials,12 respectively. The diagnosis of polycythemia vera is facilitated by applying the WHO diagnostic criteria (Figure 2);1 however, one should be aware of atypical presentations, including “masked” polycythemia vera,30 as well as the development of thrombosis at atypical sites.26
Optimal management strategies must include the frequent assessment of symptom burden and its effect on a patient’s QoL, with a keen awareness of the nonspecific nature of polycythemia vera–related symptoms, and the potential for patients and clinicians to minimize that effect.20 Patient-reported symptom severity and QoL should be assessed at each office visit with validated instruments, such as the MPN-SAF 10-item questionnaire.22It is important for the community oncologist to define treatment goals and implement a plan that reduces disease-associated morbidity and mortality. A critical treatment goal is to maintain hematocrit <45% by the appropriate use of phlebotomy12 and/or cytoreductive agents.12,16,46 Continued reassessment is important to identify patients with progressive disease and those who fail to achieve stated treatment goals or require an adjustment in cytoreductive therapy. Oncologists should be familiar with the concept of hydroxyurea resistance/intolerance as defined by the ELN (Table)31,45 to allow early identification of those patients who are most likely to benefit from a treatment change for continued optimal outcome.
Conclusions
Polycythemia vera is a clonal myeloproliferative neoplasm associated with significant disease-related morbidity and mortality. Appropriate management includes early diagnosis and implementation of appropriate therapy according to patient risk and therapeutic tolerance. Patients should initially receive aspirin32 and phlebotomy,12 with the goal of maintaining hematocrit <45%. Higher-risk patients and those who had inadequate disease control with phlebotomy alone require cytoreduction, typically with hydroxyurea. Although most patients will achieve adequate disease control with hydroxyurea,33,43 one in four patients will develop drug resistance or intolerance.44 Ruxolitinib is approved by the FDA and the EMA for the treatment of patients with polycythemia vera who are resistant to or intolerant of hydroxyurea. Compared with BAT, ruxolitinib is associated with improved hematocrit control, reductions in spleen size, a greater probability of blood count normalization, and improvement in polycythemia vera–related symptoms.16
Acknowledgments
Writing assistance was provided by Cory Pfeiffenberger, PhD, of Complete Healthcare Communications LLC, and was funded by Incyte Corporation, the maker of ruxolitinib.
