Long-Term Safety Profile of Ruxolitinib in Chronic Myeloproliferative Neoplasms: A Comprehensive Real-World Analysis

Ruxolitinib is a key therapeutic option for patients with myeloproliferative neoplasms. Its short-term toxicity profile is well-established, but long-term safety data remains scarce.

We aimed to evaluate toxicity associated with long-term exposure to ruxolitinib (defined as 3 years or longer) through a dual-cohort retrospective study combining a local cohort from Hospital 12 de Octubre with a large real-world dataset from TriNetX database. The selected outcomes were non-melanoma skin cancer (NMSC), other secondary malignancies and infections (zoster, urinary tract infection, pneumonia and sepsis).

With a median treatment time of 61.5 months in the local cohort (n = 36), infections were common (72.2% of patients), with occurrence of late-onset opportunistic infections such as disseminated mycobacterial disease. A total of 19.4% of patients developed NMSC and 11.1% other secondary malignancies. In the TriNetX cohort, after propensity score matching (n = 2579), patients with ≥ 3 years of ruxolitinib showed a higher risk of NMSC, zoster, urinary tract infection, pneumonia and sepsis. No significant increase in other tumours was observed.

Our findings suggest that extended ruxolitinib therapy is associated with specific long-term risks, particularly NMSC and zoster reactivation, while not increasing the incidence of secondary malignancies. These results support continued vigilance and preventive strategies in the setting of long-term ruxolitinib exposure.

The authors have confirmed clinical trial registration is not needed for this submission.