Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis.

Abstract

Ruxolitinib is a potent Janus kinase (JAK)1/JAK2 inhibitor that has demonstrated rapid reductions in splenomegaly and marked improvement in disease-related symptoms and quality of life in patients with myelofibrosis (MF). The present analysis reports the 3-year follow-up (median, 151 weeks) of the efficacy and safety of Controlled Myelofibrosis Study With Oral Janus-associated Kinase (JAK) Inhibitor Treatment-II (the COMFORT-II Trial), comparing ruxolitinib with the best available therapy (BAT) in 219 patients with intermediate-2 and high-risk MF. In the ruxolitinib arm, with continued therapy, spleen volume reductions of ≥35% by magnetic resonance imaging (equivalent to approximately 50% reduction by palpation) were sustained for at least 144 weeks, with the probability of 50% (95% confidence interval [CI], 36-63) among patients achieving such degree of response. At the time of this analysis, 45% of the patients randomized to ruxolitinib remained on treatment. Ruxolitinib continues to be well tolerated. Anemia and thrombocytopenia were the main toxicities, but they were generally manageable, improved over time, and rarely led to treatment discontinuation (1% and 3.6% of patients, respectively). No single nonhematologic adverse event led to definitive ruxolitinib discontinuation in more than 1 patient. Additionally, patients randomized to ruxolitinib showed longer overall survival than those randomized to BAT (hazard ratio, 0.48; 95% CI, 0.28-0.85; log-rank test, P = .009).

• Authors: Francisco Cervantes, Alessandro M Vannucchi, Jean-Jacques Kiladjian, Haifa Kathrin Al-Ali, Andres Sirulnik, Viktoriya Stalbovskaya, Mari McQuitty, Deborah S Hunter, Richard S Levy, Francesco Passamonti, Tiziano Barbui, Giovanni Barosi, Claire N Harrison, Laurent Knoops, Heinz Gisslinger, COMFORT-II investigators
• Journal: Blood (Blood) Vol. 122 Issue 25 Pg. 4047-53 (Dec 12 2013) ISSN: 1528-0020 [Electronic] United States
• PMID: 24174625 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Nitriles
• Protein Kinase Inhibitors
• Pyrazoles
• Pyrimidines
• ruxolitinib
• JAK1 protein, human
• JAK2 protein, human
• Janus Kinase 1
• Janus Kinase 2

Topics

• Anemia (chemically induced, drug therapy, enzymology, mortality)
• Disease-Free Survival
• Female
• Follow-Up Studies
• Humans
• Janus Kinase 1 (antagonists & inhibitors)
• Janus Kinase 2 (antagonists & inhibitors)
• Male
• Nitriles
• Primary Myelofibrosis (drug therapy, enzymology, mortality)
• Protein Kinase Inhibitors (administration & dosage, adverse effects)
• Pyrazoles (administration & dosage, adverse effects)
• Pyrimidines
• Survival Rate
• Thrombocytopenia (chemically induced, drug therapy, enzymology, mortality)
• Time Factors