Second primary malignancy in myelofibrosis patients treated with ruxolitinib

Ruxolitinib (RUX), the first JAK1/JAK2 inhibitor approved for myelofibrosis (MF) therapy, has recently been associated with the occurrence of second primary malignancies (SPMs), mainly lymphomas and non-melanoma skin cancers (NMSCs). We analyzed the incidence, risk factors and outcome of SPMs in 700 MF patients treated with RUX in a real-world context. Median follow-up from starting RUX was 2 center dot 9 years. Overall, 80 (11 center dot 4%) patients developed 87 SPMs after RUX start. NMSCs were the most common SPMs (50 center dot 6% of the cases). Multivariate analysis demonstrated that male sex [hazard ratio (HR): 2 center dot 37, 95% confidence interval (95%CI): 1 center dot 22-4 center dot 60, P = 0 center dot 01] and thrombocytosis> 400 x 10(9)/l at RUX start (HR:1 center dot 98, 95%CI: 1 center dot 10-4 center dot 60, P = 0 center dot 02) were associated with increased risk for SPMs. Risk factors for NMSC alone were male sex (HR: 3 center dot 14, 95%CI: 1 center dot 24-7 center dot 92, P = 0 center dot 02) and duration of hydroxycarbamide and RUX therapy > 5 years (HR: 3 center dot 20, 95%CI: 1 center dot 17-8 center dot 75, P = 0 center dot 02 and HR: 2 center dot 93, 95%CI: 1 center dot 39-6 center dot 17, P = 0 center dot 005 respectively). In SPMs excluding NMSCs, male sex (HR: 2 center dot 41, 95%CI: 1 center dot 11-5 center dot 25, P = 0 center dot 03), platelet > 400 x 10(9)/l (HR: 3 center dot 30, 95%CI: 1 center dot 67-6 center dot 50, P = 0 center dot 001) and previous arterial thromboses (HR: 3 center dot 47, 95%CI: 1 center dot 48-8 center dot 14, P = 0 center dot 004) were shown to be associated with higher risk of SPMs. While it is reassuring that no aggressive lymphoma was documented, active skin surveillance is recommended in all patients and particularly after prolonged hydroxycaramide therapy; oncological screening should be triggered by thrombocytosis and arterial thrombosis, particularly in males.

Automated summary

RUX treatment has been associated with a higher incidence of SPMs, with NMSCs being the most common. Risk factors for SPMs include male sex and thrombocytosis at RUX start. For SPMs excluding NMSCs, male sex, thrombocytosis, and previous arterial thromboses are considered high-risk factors.