Work

P1062: Indirect Treatment Comparison of Momelotinib Vs Fedratinib Safety in Patients With Myelofibrosis

Year: 2023

Type: article

Abstract: Topic: 16. Myeloproliferative neoplasms - Clinical Background: JAK inhibitors (JAKi) are a mainstay of myelofibrosis (MF) treatment, with proven ability to improve symptoms and spleen volume for most patients (pts); although safety profiles vary, some approved JAKi have associated hematologic toxicity. The JAK1/JAK2/ACVR1 inhibitor momelotinib (MMB) has shown consistent benefit in improving anemia, symptoms, and spleen volume in pts with MF. Clinical trials have directly compared MMB with ruxolitinib, with MMB showing a more favorable hematologic toxicity profile. However, there are limited data comparing MMB vs other JAKi such as fedratinib (FED). Aims: To compare safety outcomes from phase 2 and/or 3 MMB and FED trials using matching-adjusted indirect comparison (MAIC). Methods: Adverse events (AEs) occurring in >10% of a treatment arm were evaluated; primary outcomes were grade 3/4 anemia and thrombocytopenia. Separate analyses were performed in JAKi-naive (SIMPLIFY-1 [S1] vs JAKARTA) and JAKi-experienced (pooled SIMPLIFY-2 [S2], MOMENTUM vs JAKARTA2) pts. Evaluable outcomes were those with published data for FED. MAIC involved reweighting MMB pt data to match baseline characteristics prioritized by expert clinical input (DIPSS/IPSS, Total Symptom Score, platelet counts, spleen volume/length, and/or hemoglobin levels) between trial arms, and estimating odds ratios (ORs), risk ratios, and risk differences (RDs) to compare AE rates between balanced populations. As nonrandomized groups were compared, results may be biased due to unmeasured confounding, despite adjusting for clinically relevant confounding factors. Sensitivity analyses were conducted to account for differences in lengths of follow-up time for AE reporting where reporting of the assessment periods was unclear. Results: Effective MMB sample sizes after adjustment were 151.1 JAKi-naive and 79.4 JAKi-experienced pts. Odds of any or grade 3/4 anemia, any grade diarrhea, any grade nausea, and serious AEs leading to dose reductions were statistically less likely with MMB vs FED in both populations; any or grade 3/4 thrombocytopenia was also less likely with MMB vs FED, significantly so in JAKi-naive pts. Odds of other outcomes assessed varied in significance (Table). Compared with FED in JAKi-naive pts, MMB was associated with significantly lower risk of any or grade 3/4 anemia, any grade thrombocytopenia, any grade diarrhea, any grade nausea, grade 3/4 AEs, serious AEs, and serious AEs leading to dose reduction; risk of grade 3/4 thrombocytopenia and serious AEs leading to treatment discontinuation were both also numerically lower for MMB than FED. Compared with FED in JAKi-experienced pts, MMB was associated with significantly lower risk of any or grade 3/4 anemia, any grade diarrhea, any grade nausea, and serious AEs leading to treatment discontinuation or dose reduction (Table). No identified outcomes were statistically favorable for FED. Summary/Conclusion: MMB showed a favorable safety profile vs FED, in terms of AE rates reported in registrational clinical trials, in both JAKi-naive and experienced pts, including a significantly lower risk of anemia, diarrhea, and nausea. TableKeywords: Myeloproliferative disorder, Janus Kinase inhibitor, Myelofibrosis, Safety

Source: HemaSphere

DOI: 10.1097/01.hs9.0000971144.30344.9c