Diagnosis and Management of Polycythemia Vera in the Post-JAK2 V617F Discovery Era: A Survey of Practice Patterns

Background and Methods

The identification of JAK2 V617F ushered in a new era of discovery in polycythemia vera (PV) resulting in improved diagnostic capability, better understanding of pathogenesis, and development of JAK inhibitors (JAKi). In 2002, a survey of PV practice patterns among ASH members reported that the most commonly used diagnostic tests were red cell mass (RCM) studies, erythropoietin (epo) levels, and arterial blood gases. Most respondents used a target Hct ≤ 44%, though 16% used a target of 50 or 55%. While most treated a platelet (plt) count of > 1000 x 10⁹/L, a significant number used a lower threshold, or treated only those with symptomatic thrombocytosis (12%). Hydroxyurea (HU) was most commonly used to treat thrombocytosis and 55% and 15% percent of respondents avoided interferon (IFN), and aspirin (ASA), respectively as treatments for thrombocytosis. Practice patterns and perceptions regarding safety and efficacy of therapy in the post-JAK2 discovery era are unknown. Therefore, registrees from the MPN Research Foundation (MPNRF; N=850) or MDS/Aplastic Anemia Foundation (N=13,445) were invited by email to complete an institutional review board-approved survey consisting of 17 questions. Fisher’s exact test was used to compare responses (p <0.05 considered statistically significant).

Results

Seventy-two responded, including 67 from MPNRF (7.8%). Most (83%) considered themselves a hematologist, and 85% practiced in an academic setting. Fifty-one % had > 16 years (yrs) of experience after training and 46% reported having > 16 PV patients in their practice (the number of patients in practice did not influence responses). Respondents reported that the complete blood count (CBC) (94%), JAK2 V617F (91%), and epo level (84%) were the most useful diagnostic tests. Bone marrow aspirate/biopsy was considered more useful than RCM (57% vs. 23%; p <0.0001). A trend toward greater use of RCM among hematologists rather than oncologists was noted. (26% vs. 0%; p=0.057) Seventy-six % characterized PV as a blood neoplasm; the next most common characterization was as a “blood disorder or syndrome” (24%). Respondents from academic and private practices also characterized PV this way, but in different proportions (81% and 50% as a blood neoplasm, respectively p=0.047). Forty-seven % used a gender-dependent Hct target (<42% (women) and < 45% (men)) for phlebotomy (PBT), whereas 41% used Hct <45% universally. Hct targets of < 50% (8.8%) or < 55% (2.9%) were less common. While 79% recommended ASA for all, unless contraindicated, respondents with > 16 yrs of experience were less likely to universally recommend ASA (69%, 25/36), compared to those with fewer yrs of experience (91%, 29/32). (p=0.039) Regardless of practice setting, the most common plt goals were < 400 x 10⁹/L (34%) or 400-600 x 10⁹/L (34%), and 26% treated thrombocytosis only in the presence of symptoms. Thrombosis history (75%), microvascular disturbance (73%), and age > 60 (59%) were the most common indications for cytoreduction. HU was the preferred cytoreductant (89%); 50% prescribed HU regardless of age, whereas 34% avoided use in those < 40 yrs. Respondents with > 16 yrs experience were more likely to prescribe HU regardless of age compared to those less experienced (67% vs. 31%, p=0.007). Thirty % believed that HU could accelerate development of leukemia and 28% believed that anagrelide could accelerate myelofibrosis. Respondents most commonly avoided P³² (74%), busulfan (67%), and recombinant (rIFN) (36%) due to side effects. Respondents (23 did not answer) believed that peg-IFN (67%), rIFN (49%), and JAKi (43%) had potential to modify the natural history of PV. Respondents perceived that JAKi would be most useful in improving symptoms (84%), reducing splenomegaly (79%), and decreasing PBT needs (60%); fewer believed in its potential to prolong survival (36%) or cure PV (9%), respectively.

Conclusion

Variation in the management of PV remains, especially regarding the influence of gender on the Hct target, age restriction for HU use, requirement for ASA, and ideal platelet goal. Respondents perceive that JAKi may ameliorate symptoms, treat splenomegaly, and decrease PBT needs, and are optimistic regarding the potential of peg-IFN. Physicians would benefit from consensus-driven, evidence-based guidelines to help manage PV.