In the phase III SIMPLIFY-1 noninferiority trial reported in the Journal of Clinical Oncology, Mesa et al found that the selective Janus kinase (JAK) 1 and 2 inhibitor momelotinib was noninferior to ruxolitinib (Jakafi) in spleen response, but not symptom response, in JAK inhibitor–naive patients with myelofibrosis.
In the trial, 432 patints with high-risk, intermediate-2 risk, or symptomatic intermediate-1 risk myelofibrosis were randomized to receive 24 weeks of double-blind treatment with momelotinib at 200 mg once daily (n = 215) or ruxolitinib at 20 mg twice daily (n = 217), after which patients could receive open-label momelotinib. The primary endpoint was a ≥ 35% reduction in spleen volume at 24 weeks (spleen response), as assessed by magnetic resonance imaging or computed tomography by a blinded central reader.
Spleen response at 24 weeks was observed in 26.5% of the momelotinib group vs 29% of the ruxolitinib group (P = .011 for noninferiority). Noninferiority was not achieved in symptom response (≥ 50% reduction in total symptom score), observed in 28.4% vs 42.2% of patients (P = .98 for noninferiority). At week 24, transfusion independence (66.5% vs 49.3%, nominal P < .001), transfusion dependence (30.2% vs 40.1%, nominal P = .019), and red blood cell transfusion rate (median 0 units/month vs 0.4 units/month, nominal P < .001) were significantly better in the momelotinib group.
Grade ≥ 3 adverse events occurred in 35.5% of the momelotinib group vs 43.5% of the ruxolitinib group; the most common adverse events with momelotinib were thrombocytopenia (7.0%), anemia (5.6%%), and diarrhea, hypertension, and neutropenia (2.8% each), and the most common adverse events with ruxolitinib were anemia (23.1%), neutropenia and thrombocytopenia (4.6% each), and hypertension (4.2%). Grade ≥ 3 infection occurred in 7% vs 3%. Peripheral neuropathy occurred in 10% (all grade ≤ 2) vs 5% (all grade ≤ 3).
The investigators concluded: “In [JAK inhibitor]-naive patients with myelofibrosis, 24 weeks of momelotinib treatment was noninferior to ruxolitinib for spleen response but not for symptom response. Momelotinib treatment was associated with a reduced transfusion requirement.”
The study was supported by Gilead Sciences.
Ruben A. Mesa, MD, of the Mayo Clinic Cancer Center, Phoenix, is the corresponding author of the Journal of Clinical Oncology article.
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