Ruxolitinib long-term safety in chronic MPN: Real-world data

Real-world data from a dual-cohort retrospective study, evaluating the safety of long-term (≥3 years) ruxolitinib exposure in patients with chronic myeloproliferative neoplasms (MPN), were recently published in the European Journal of Haematology by Blanco-Sánchez et al. The study combined a local cohort (n = 36 total: n = 11 with primary myelofibrosis [MF]; n = 18 with secondary MF; n = 5 with polycythemia vera [PV]; n = 2 with essential thrombocythemia [ET]) with TriNetX electronic medical records real-world data (n = 1,368 with ≥3 years exposure; n = 2,579 after 1:1 propensity score matching). The selected outcomes were non-melanoma skin cancer (NMSC), other secondary malignancies, and infections.

Key data: With a median exposure of 61.5 months (range, 36–151 months) in the local cohort, 72.2% of patients developed infections, 19.4% of patients developed NMSC, and 11.1% developed other secondary malignancies; 27.3% of patients developed Grade 3–4 infections. With a median exposure of 66.3 months (interquartile range [IQR], 49.3–88.8) in the TriNetX cohort, after propensity score matching (n = 2,579), patients with ≥3 years of ruxolitinib exposure showed significantly (p < 0.05) increased risk of NMSC (hazard ratio [HR], 1.67; confidence interval [CI], 1.35–2.08), herpes zoster (HR, 3.29; CI, 2.33–4.66), pneumonia (HR, 1.51; CI, 1.26–1.79), urinary tract infection (UTI; HR, 1.33; CI, 1.11–1.60), and sepsis (HR, 1.45; CI, 1.17–1.80). No significant increase in other secondary malignancies or lymphoma was observed.

Key learning: Long-term ruxolitinib exposure (≥3 years) is associated with long-term risks, including increased risk of NMSC and specific infections, particularly herpes zoster reactivation, but not other secondary malignancies, supporting the need for continued surveillance and preventive strategies in long-term users.