Prevalence, incidence, and risk factors of secondary malignancies in patients with polycythemia vera: a real-world study.

Patients with the primary myeloproliferative neoplasm polycythemia vera (PV) are at risk of the development of secondary malignancies, including skin cancers. This real-world, retrospective cohort study used Optum Market Clarity electronic health record data and linked medical and pharmacy claims from 70 million patients in the United States between 1 January 2007 and 31 December 2019 to assess the frequency of secondary malignancies in patients with a new or established diagnosis of PV (N = 82 947 with ≥1 PV diagnosis; the final cohort for this study included 20 089 patients) and the association of these cancers with patient characteristics and PV treatment. After indexing, 36% of patients had at least 1 non-PV malignancy (follow-up duration, 4.3 years). The most common nonhematologic malignancies were skin cancers, including melanoma and nonmelanoma skin cancer (NMSC). The incidence rate for a composite outcome of new-onset melanoma or NMSC was nearly twofold higher in patients who were exposed to hydroxyurea at any time than in those who were exposed to therapeutic phlebotomy alone. The strongest risk factors for occurrence of melanoma or NMSC in the observation period included older age, previous history of skin cancer, and preindex period use of cytoreductive medications. After controlling for potential confounders, a higher likelihood of developing new-onset melanoma or NMSC was observed in patients who received ≥4 weeks of hydroxyurea exposure vs those with no hydroxyurea exposure (hazard ratio, 1.33; 95% confidence interval, 1.17-1.50). This finding, which may have been influenced by different disease burdens among this diverse patient population, warrants further exploration.