Long-term treatment with ruxolitinib for patients with myelofibrosis: 5-year update from the randomized, double-blind, placebo-controlled, phase 3 COMFORT-I trial

• Published in: Journal of hematology and oncology 2017-02, Vol.10 (1), p.55-14, Article 55
• Main Authors: Verstovsek, Srdan, Mesa, Ruben A, Gotlib, Jason, Gupta, Vikas, DiPersio, John F, Catalano, John V, Deininger, Michael W N, Miller, Carole B, Silver, Richard T, Talpaz, Moshe, Winton, Elliott F, Harvey, Jr, Jimmie H, Arcasoy, Murat O, Hexner, Elizabeth O, Lyons, Roger M, Paquette, Ronald, Raza, Azra, Jones, Mark, Kornacki, Deanna, Sun, Kang, Kantarjian, Hagop
• Format: Article
• Language: English
• Subjects: Analysis; Anemia; Diarrhea - chemically induced; Disease Progression; Dosage and administration; Double-Blind Method; Drug dosages; Drug therapy; Fatigue - chemically induced; FDA approval; Follow-Up Studies; Hematology; Hemoglobin; Humans; JAK; Janus kinase; Janus Kinases - antagonists & inhibitors; Kinases; Mutation; Myelofibrosis; Oncology; Pneumonia - chemically induced; Primary Myelofibrosis - complications; Primary Myelofibrosis - drug therapy; Primary Myelofibrosis - mortality; Pyrazoles - administration & dosage; Pyrazoles - adverse effects; Pyrazoles - therapeutic use; Risk Assessment; Ruxolitinib; Sepsis - chemically induced; Spleen; Splenomegaly - drug therapy; Survival Rate; Thrombocytopenia; Transplants & implants; Treatment Outcome
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/s13045-017-0417-z

The randomized, double-blind, placebo-controlled, phase 3 COMFORT-I trial evaluated the JAK1/JAK2 inhibitor ruxolitinib in patients with intermediate-2/high-risk myelofibrosis. The primary and planned 3-year analyses of COMFORT-I data demonstrated that ruxolitinib-the first myelofibrosis-approved therapy-reduced splenomegaly and prolonged overall survival versus placebo. Here, we present the final 5-year results. Patients managed in Australia, Canada, and the USA were randomized centrally (interactive voice response system) 1:1 to oral ruxolitinib twice daily (15 or 20 mg per baseline platelet counts) or placebo. Investigators and patients were blinded to treatment. The secondary endpoints evaluated in this analysis were durability of a ≥35% reduction from baseline in spleen volume (spleen response) and overall survival, evaluated in the intent-to-treat population. Safety was evaluated in patients who received study treatment. Patients were randomized (September 2009-April 2010) to ruxolitinib (n = 155) or placebo (n = 154). At termination, 27.7% of ruxolitinib-randomized patients and 25.2% (28/111) who crossed over from placebo were on treatment; no patients remained on placebo. Patients randomized to ruxolitinib had a median spleen response duration of 168.3 weeks and prolonged median overall survival versus placebo (ruxolitinib group, not reached; placebo group, 200 weeks; HR, 0.69; 95% CI, 0.50-0.96; P = 0.025) despite the crossover to ruxolitinib. The ruxolitinib safety profile remained consistent with previous analyses. The most common new-onset all-grade nonhematologic adverse events starting