Begna, Kebede H.

AbstractWe retrospectively reviewed 72 anemic patients with myelofibrosis (MF; median age 68 years), who were JAK2 inhibitor‐naïve at the time of study entry to a phase‐1/2 momelotinib clinical trial. Driver mutation profile included JAK2 69%, CALR 17%, MPL 8%, and triple‐negative 6%; other mutations included ASXL1 39% and SRSF2 17%. Momelotinib was administered at a median dose of 300 mg daily. Anemia response was assessed by formal criteria and documented in 44% of all patients with hemoglobin levels below the sex‐adjusted reference range (n = 72), 48% of those with hemoglobin <10 g/dl (n = 54), and 46% of those who were transfusion‐dependent at the time of study entry (n = 28). Anemia response was more likely with post‐essential thrombocythemia MF (83% vs 37%; p = .001), lower serum ferritin (p = .003), and shorter time from diagnosis to momelotinib therapy (p = .001); the first two variables were also predictive in transfusion‐dependent patients. Post‐momelotinib median survival was 3.2 years; in univariate analysis, survival was superior in anemia responders (median 3.8 vs. 2.8 years; p = .14) and in the presence of type 1/like CALR mutation and inferior in the presence of age > 65 years, ASXL1/SRSF2 mutation, unfavorable karyotype, DIPSS‐plus high risk, red cell transfusion need and higher serum ferritin. Multivariable analysis confirmed the favorable impact of anemia response on survival (p = .02; HR 0.5, 3/5/10‐year survival; 69%/38%/25%). This survival advantage was also noted in transfusion‐dependent patients (3.7 vs. 1.9 years; p = .01; HR 0.3) and appeared to be restricted to patients with an unfavorable genetic profile. The current study suggests a short‐term survival benefit associated with anemia response in momelotinib‐treated patients with MF.