Polycythemia vera (PV) is a Philadelphia chromosome-negative myeloproliferative neoplasm caused by the JAK2 V617F (or, in rare cases, exon 12) mutation. Its natural history can last several decades; therefore, treatment planning is based on a continuous appraisal of conventional risk factors (age, past thrombosis) to determine the necessity for cytoreduction in addition to fundamental therapy with low-dose aspirin and rigorous phlebotomy.
Short- and long-term patient objectives should take into account a variety of considerations, including concomitant diseases (particularly cardiovascular risk factors), disease symptoms, and the risk-benefit balance of available medications. While hydroxyurea has long been the go-to cytoreduction agent for many practitioners, recent regulatory approvals of ruxolitinib and peginterferon-alfa-2b based on phase 3 randomized studies indicate a growing array of active medications. Most studies may get high-level evidence for short-term clinical trial outcomes such as hematocrit control, symptom burden/quality of life, splenomegaly, and JAK2 V617F allele burden.
However, in many circumstances, it may be unable to appropriately power studies to detect significant changes in the normally modest thrombosis event rates, as well as longer-term outcomes such as progression to myelofibrosis, acute myeloid leukemia, and survival. The Perspective addresses the difficulty of filling data gaps and answering unanswered concerns in the PV treatment environment as it emerges.
