Momelotinib (Ojjaara) has shown improved overall survival (OS) compared to best available therapy (BAT) in patients with myelofibrosis previously treated with ruxolitinib (Jakafi), according to data presented at the 2024 ASH Annual Meeting & Exposition. The findings come from a matching-adjusted indirect comparison (MAIC) analysis.
The unmatched analysis demonstrated a significant median OS benefit for patients receiving momelotinib (n = 383) compared to those receiving BAT (n = 267), with a hazard ratio (HR) of 0.373 (95% CI, 0.297-0.469; P < .001). In the base case model (model 1), the median OS also favored momelotinib (n = 89) vs BAT (HR, 0.512; 95% CI, 0.358-0.732; P < .001). The alternative adjustment model (model 2) similarly favored momelotinib (n = 117) vs BAT (HR, 0.484; 95% CI, 0.347-0.675; P < .001).
Anemia Subgroup Analysis
Patients in the anemia subgroup who received momelotinib (n = 255) also experienced a median OS benefit compared to those treated with BAT (n = 174; HR, 0.384; 95% CI, 0.293-0.504; P < .001). Model 1 showed a median OS benefit in the momelotinib arm (n = 98) vs BAT (HR, 0.542; 95% CI, 0.387-0.759; P < .001), and model 2 also demonstrated a median OS benefit with momelotinib (n = 146) vs BAT (HR, 0.487; 95% CI, 0.360-0.660; P < .001).
Dr. Francesca Palandri, lead study author and an adjunct professor at the University of Bologna in Italy, noted that while the trials used in the analysis do not provide long-term outcomes, the MAIC suggests momelotinib may offer a greater OS benefit than BAT in ruxolitinib-pretreated myelofibrosis patients, both overall and in the anemic population.
Background on Momelotinib
In September 2023, the FDA approved momelotinib for treating adult patients with intermediate or high-risk myelofibrosis, including primary or secondary myelofibrosis, and anemia. This approval was based on the phase 3 MOMENTUM and SIMPLIFY-1 trials.
MAIC Analysis Details
The MAIC analysis compared patients from the MOMENTUM, SIMPLIFY-1, and SIMPLIFY-2 trials who received momelotinib with 267 patients who received BAT across 26 European hematology centers in the RUX-MF study. The RUX-MF study included 1055 patients treated with ruxolitinib from 2013 until the data cutoff in February 2024.
Eligible patients had myelofibrosis and received momelotinib or BAT as second-line therapy. BAT included hydroxyurea, danazol, corticosteroids, erythropoiesis-stimulating agents, and other investigational agents. The comparison was limited to patients in the chronic phase. The anemic subgroup was defined as patients with hemoglobin levels less than 10 g/dL.
Patients receiving momelotinib were reweighted using two models with different matching factors to align with the BAT population. Both models used patient age, sex, BMI, myelofibrosis subtype, and Dynamic International Prognostic Scoring System for Myelofibrosis risk score. Model 1 also included hemoglobin levels, white blood cell counts, spleen length, and total symptom score.
The mean patient age was 71.5 years across the BAT group, model 1, and model 2. Most patients were male (58.4%), had primary myelofibrosis (51.7%), and had hemoglobin levels less than 10 g/dL (65.2% in BAT group; 65.2% in model 1; 67.3% in model 2). High-risk disease was present in 15.4% of patients in each arm, and 51.7% had intermediate-2-risk disease.
Sensitivity Analyses
Additional analyses, excluding patients randomly assigned to ruxolitinib in SIMPLIFY-1, still showed a median OS benefit with momelotinib over BAT in both model 1 (HR, 0.479; 95% CI, 0.292-0.786; P = .004) and model 2 (HR, 0.512; 95% CI, 0.330-0.797; P = .003). Excluding patients randomly assigned to momelotinib in MOMENTUM also demonstrated a median OS benefit with momelotinib compared to BAT using model 1 (HR, 0.551; 95% CI, 0.379-0.800; P = .002) and model 2 (HR, 0.521; 95% CI, 0.366-0.742; P < .001).
In the anemia subgroup, excluding data from SIMPLIFY-1 or MOMENTUM consistently showed a median OS benefit with momelotinib over BAT.
Conclusion
Dr. Palandri concluded that these data, along with the results of the SIMPLIFY-2 and MOMENTUM trials, further support the use of momelotinib as a standard of care in patients with myelofibrosis and anemia in this setting.
