Clinical outcomes under hydroxyurea treatment in polycythemia vera: a systematic review and meta-analysis

Hydroxyurea is the standard treatment in high risk patients with polycythemia vera. Yet, estimates of its effect in terms of clinical outcomes (thrombosis, bleeding, hematological transformations and mortality) are lacking. We performed a meta-analysis to determine the absolute risk of events in contemporary patients under hydroxyurea treatment. We searched for relevant articles or abstracts in the following databases: Medline, EMBASE, clinicaltrials.gov, WHO International Clinical Trials Registry, LILACS. Sixteen studies published from 2008 to 2018 reporting number of events using WHO diagnosis for polycythemia vera were selected. Through a random effect logistic model, incidences, study heterogeneity and confounder effects were estimated for each outcome at different follow-ups. Overall, 3,236 patients were analyzed. While incidences of thrombosis and acute myeloid leukemia were stable over time, mortality and myelofibrosis varied depending on follow-up duration. Thrombosis rates were 1.9, 3.6 and 6.8% persons/year at median ages 60, 70 and 80 respectively. Higher incidence of arterial events was predicted by previous cardiovascular complication. Leukemic transformation incidence was 0·4% persons/year. Incidence of transformation to myelofibrosis and mortality were significantly dependent on age and follow-up duration. For myelofibrosis, rates were 5.0 at 5 year and 33.7% at 10 years; overall mortality was 12.6% and 56.2% at 5 and 10 years respectively. In conclusion, we provide reliable risk estimates for the main outcomes in polycythemia vera patients under hydroxyurea treatment. These findings can help design comparative clinical trials with new cytoreductive drugs and prove the feasibility of using hard endpoints for efficacy, such as major thrombosis.