Efficacy and safety of fedratinib in myelofibrosis patients after ruxolitinib: A systematic review and meta-analysis.

Abstract

e18592 Background: Myelofibrosis is a rare myeloproliferative neoplasm characterized by bone marrow fibrosis, splenomegaly, and debilitating symptoms. Fedratinib (FED), a selective JAK2/FLT3 inhibitor, has emerged as a therapeutic option for patients with myelofibrosis, particularly in those relapsed/refractory or intolerant patients to ruxolitinib (RUXO). This meta-analysis synthesizes evidence on the efficacy and safety of FED in post-RUXO settings, aiming to provide robust insights for clinical decision-making and optimize patient outcomes. Methods: PubMed, Cochrane CENTRAL, and Embase were systematically searched from inception to December 30, 2024. Randomized or non-randomized clinical trials, and prospective or retrospective cohort studies evaluating FED after RUXO treatment were included. Spleen volume reduction, symptom response rate, treatment-related adverse events, and treatment discontinuation were assessed. We computed event rates with 95% confidence intervals (C.I.) when assessing FED in a single-arm analysis while we calculated risk ratios with 95% C.I. when conducting double-arm analyses comparing FED after RUXO with treatment with RUXO alone. Statistical analyses using a fixed-effects model were done using Comprehensive Meta-Analysis and Review Manager. Results: The analysis included 8 studies enrolling 960 participants receiving fedratinib after prior treatment with ruxolitinib for myelofibrosis. The mean age ranged from 56 to 73 years. In the treatment group, the event rate for a 35% reduction in spleen volume at 6 months was 39.2% (C.I. 0.33-0.45, p = 0.001), and the symptom response rate was 31.5% (C.I. 0.25-0.40, p < 0.001). The treatment discontinuation rate was 17.1% (C.I. 0.13-0.22, p<0.001). Grade ¾ treatment-related adverse events were calculated to be 41.2% (C.I. 0.34-0.48, p = 0.016). Adverse events analyzed included diarrhea [29.0% (C.I. 0.25-0.33, p < 0.001)], thrombocytopenia [21.6% (C.I. 0.18-0.26, p < 0.001)], and anemia [31.2% (C.I. 0.27-0.36, p < 0.001)]. When FED after RUXO was compared with RUXO alone, the risk for thrombocytopenia [RR 0.96 (C.I. 0.39-2.36, p = 0.93)] and anemia [RR 0.85 (C.I. 0.69-1.05, p = 0.14)] was similar. Conclusions: This meta-analysis supports the use of FED after prior treatment with RUXO among patients with myelofibrosis given its beneficial effects in reducing spleen volume and improving symptoms whilst having a comparable adverse events profile.