Efficacy, safety, and survival with ruxolitinib in patients with myelofibrosis: Results of a median 3-year follow-up of COMFORT-I

Srdan Verstovsek, Ruben A. Mesa, Jason Gotlib, Richard S. Levy, Vikas Gupta, John F. Dipersio, John V. Catalano, Michael W.N. Deininger, Carole B. Miller, Richard T. Silver, Moshe Talpaz, Elliott F. Winton, Jimmie H. Harvey, Murat O. Arcasoy, Elizabeth O. Hexner, Roger M. Lyons, Azra Raza, Kris Vaddi, William Sun, Wei PengVictor Sandor, Hagop Kantarjian

Research output: Contribution to journalArticle

152 Scopus citations

Abstract

In the phase III COMFORT-I study, the Janus kinase 1 (JAK1)/JAK2 inhibitor ruxolitinib provided significant improvements in splenomegaly, key symptoms, and quality-of-life measures and was associated with an overall survival benefit relative to placebo in patients with intermediate-2 or high-risk myelofibrosis. This planned analysis assessed the long-term efficacy and safety of ruxolitinib at a median follow-up of 149 weeks. At data cutoff, approximately 50% of patients originally randomized to ruxolitinib remained on treatment whereas all patients originally assigned to placebo had discontinued or crossed over to ruxolitinib. At week 144, mean spleen volume reduction was 34% with ruxolitinib. Previously observed improvements in quality-of-life measures were sustained with longer-term ruxolitinib therapy. Overall survival continued to favor ruxolitinib despite the majority of placebo patients crossing over to ruxolitinib [hazard ratio 0.69 (95% confidence interval: 0.46-1.03); P=0.067]. Exploratory analyses suggest that crossover may have contributed to an underestimation of the true survival difference between the treatment groups. Ruxolitinib continued to be generally well tolerated; there was no pattern of worsening grade ≥3 anemia or thrombocytopenia with longer-term ruxolitinib exposure. These longer-term data continue to support the efficacy and safety of ruxolitinib in patients with myelofibrosis.

Original languageEnglish (US)
Pages (from-to)479-488
Number of pages10
JournalHaematologica
Volume100
Issue number4
DOIs
StatePublished - 2015
Externally publishedYes

ASJC Scopus subject areas

  • Hematology

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    Verstovsek, S., Mesa, R. A., Gotlib, J., Levy, R. S., Gupta, V., Dipersio, J. F., Catalano, J. V., Deininger, M. W. N., Miller, C. B., Silver, R. T., Talpaz, M., Winton, E. F., Harvey, J. H., Arcasoy, M. O., Hexner, E. O., Lyons, R. M., Raza, A., Vaddi, K., Sun, W., ... Kantarjian, H. (2015). Efficacy, safety, and survival with ruxolitinib in patients with myelofibrosis: Results of a median 3-year follow-up of COMFORT-I. Haematologica, 100(4), 479-488. https://doi.org/10.3324/haematol.2014.115840