Second Malignancies among Older Patients with Classical Myeloproliferative Neoplasms Treated with Hydroxyurea

Patients with classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPN), including polycythemia vera (PV), essential thrombocythemia (ET), primary and secondary myelofibrosis (MF), are known to have an increased risk of second malignancies (SM). Hydroxyurea (HU) is a guideline-recommended cytoreductive therapy for high-risk MPN patients. Controversy exists as to whether HU use is associated with a higher risk of SM including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We conducted a retrospective cohort study of older patients diagnosed with MPN (age ≥66 years) in 2010-2017 and included in the Surveillance, Epidemiology, and End Results-Medicare linked database. Multivariable competing risk analyses adjusting for patient characteristics were utilized to assess the impact of HU on the development of SM. We identified 4023 patients (1688 with PV, 1976 with ET, and 359 with MF) with a median age of 77 (interquartile range [IQR]: 71-83) years at the time of MPN diagnosis. After a median follow-up of 3.25 (IQR: 2.10-5.00) years, 489 patients developed a SM (346 solid, 73 lymphoid, and 70 myeloid malignancies). The cumulative incidence probability of SM was 19.88% (95% confidence interval [CI] 17.16-22.75%) among 2683 HU users and 22.31% (95% CI: 17.51-27.47%) among 1340 non-users, respectively (Gray's test p<0.01). We did not identify significant differences in the incidence of solid or hematologic SM, including AML/MDS (HR=1.33, 95% CI: 0.77-2.29; p=0.30), between HU users and non-users. Our results suggest that the use of HU does not increase the risk of SM in older MPN patients.