Transfusion-Independence, Survival Improved in Patients with Myelofibrosis Receiving Momelotinib

Patients with myelofibrosis (MF) who received momelotinib had an increased likelihood of becoming transfusion-independent and had a lower transfusion burden than patients receiving danazol. The results of the MOMENTUM trial were presented at the 2022 American Society of Hematology Annual Meeting.

Anemia is a major unmet need in MF that is associated with poor prognosis and frequently managed with recurrent transfusions, which can reduce quality of life and overall survival (OS) as well as increase healthcare resource utilization.

Momelotinib is an oral ACVR1, JAK1, and JAK2 inhibitor that has demonstrated clinical activity on symptoms, anemia, and spleen volume in both JAK inhibitor-naïve and -experienced patients with MF.

Transfusion independence response is a common anemia endpoint, defined as the absence of transfusion and no hemoglobin <8 g/dL during the 12 weeks preceding treatment week 24. However, transfusion independence response does not fully describe transfusion burden outcomes for patients not meeting this endpoint definition. Thus, researchers in this study sought to assess the impact of momelotinib treatment on transfusion independence response, OS, and transfusion burden in JAK inhibitor-experienced patients.

The double-blind, randomized, phase III MOMENTUM study is assessing momelotinib 200 mg daily (n=130) versus danazol 600 mg daily (n=65) in patients with symptomatic MF who have previously received a JAK inhibitor. Patients received randomized treatment for 24 weeks and could then receive open-label momelotinib.

Eligible patients had primary or post-essential thrombocythemia/polycythemia vera MF; high-, intermediate-2, or intermediate-1 MF risk per the Dynamic International Prognostic Scoring System; Myelofibrosis Symptom Assessment Form total symptom score ≥10; hemoglobin <10 g/dL; prior use of a JAK inhibitor for ≥90 days or ≥28 days with red blood cell (RBC) transfusions ≥4 units in eight weeks or grade 3/4 thrombocytopenia, anemia, or hematoma; and palpable spleen ≥5 cm.

Anemia benefit was evaluated by transfusion independence response; Kaplan-Meier estimates of the proportion of patients who required zero units transfused during treatment; hazard ratio (HR) of RBC units transfused as recurrent events; HR of time to first, third, and fifth transfusion unit; and odds ratio (OR) of having zero units transfused estimated by a zero-inflated negative binomial model. Transfusion dependence was defined as requiring ≥4 units of RBC transfusions in the eight weeks immediately prior, with each transfusion in response to a hemoglobin assessment of ≤9.5 g/dL.

Mean prior JAK inhibitor treatment was 139 weeks in the momelotinib group and 125 weeks in the danazol cohort. Patients were highly anemic, with a mean hemoglobin of 8.1 g/dL in the momelotinib group and 7.9 g/dL in the danazol arm. At baseline, 48% and 49% of patients, respectively, had hemoglobin <8 g/dL. At baseline, 13% of patients in the momelotinib cohort and 15% in the danazol group were transfusion-independent, while 49% and 52%, respectively, were transfusion-dependent.

At week 24, transfusion independence response was 31% in the momelotinib group and 20% in the danazol cohort (P=.0064). During 24 weeks of treatment, 35% of patients in the momelotinib group had zero units transfused versus 17% in the danazol cohort (OR, 2.7; P=.0107).

Regardless baseline transfusion status, treatment with momelotinib resulted in fewer mean cumulative RBC units during treatment compared to the danazol cohort. Median days to first, third, and fifth transfusion was two times greater in the momelotinib group than the danazol cohort.

Among the 63 momelotinib patients who were transfusion-dependent at baseline, nine (14%) were transfusion-independent and 19% were transfusion requiring at the end of 24 weeks of treatment. Of the 34 danazol patients who were transfusion-dependent at baseline, 9% were transfusion-independent, and 9% were transfusion requiring.

The study showed that transfusion independence response was associated with prolonged OS (HR, 0.15; P=.0364).

“These findings … suggest that transfusion independence response at week 24 is a potential surrogate for improved OS,” the authors concluded.

Reference

Verstovsek S, Oh ST, Kiladjian JJ, et al. Transfusion independence response as a potential surrogate for overall survival in JAKi-experienced patients with myelofibrosis from MOMENTUM. Abstract #3028. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.