Clinical benefit and predictors of response to momelotinib after ruxolitinib failure: A cooperative real‐world study

Background: Momelotinib, a JAK1/JAK2/ACVR1 inhibitor, is approved for treatingmyelofibrosis with splenomegaly, symptoms, and moderate-to-severe anemia. Evi-dence on its real-world effectiveness after ruxolitinib failure is limited.Methods: This study retrospectively analyzed 221 patients who received momelo-tinib after ruxolitinib failure by assessing spleen, symptom, and anemia responses,safety, and survival. Logistic regression analyses identified the responses’ predictors.Results: Before momelotinib initiation, all patients had received ruxolitinib for amedian of 31.5 months and discontinued as a result of resistance (29.9%), intoler-ance (48.0%), or both (22.1%). At baseline, all patients started at full dose; 97.3%presented with cytopenia, 34.8% presented with large splenomegaly, and 43.9%were highly symptomatic. Most patients (74.7%) switched from ruxolitinib stop to momelotinib within 2 months without tapering, whereas 18.1% waited over a year.After a median exposure of 8.2 months, adverse events occurred in 35.7% of pa-tients, which prompted dose reductions or permanent discontinuation in 12.7% and19.9% of cases, respectively. At 6 months, 30.0% achieved ≥50% spleen lengthreduction (SR50), with higher responses in those with prior SR50 to ruxolitinib andshorter transition intervals. Symptom and anemia responses occurred in 39.2% and63.4% of cases, respectively. After a median follow-up of 10.3 months, 11 patients(5.0%) progressed to blast phase, and 37 patients (16.7%) died. Two-year overall andprogression-free survival (including death and blast phase transformation) were60.9% and 59.0%, respectively.Conclusions: Momelotinib demonstrated meaningful clinical benefit and acceptablesafety in cytopenic patients pretreated with ruxolitinib, which supports its role afterruxolitinib failure.