Impact of ruxolitinib on the natural history of primary myelofibrosis: a comparison of the DIPSS and the COMFORT-2 cohorts.

Abstract

The international prognostic scoring system (IPSS) provides reliable risk assessment in patients with primary myelofibrosis (PMF). Recent clinical trials in PMF patients with intermediate-2 or high IPSS risk have shown a survival advantage of ruxolitinib over placebo (COMFORT-1) or best available therapy (COMFORT-2). Because crossover was allowed in these studies, we analyzed the cohort of ruxolitinib-naive patients used for developing the dynamic IPSS (DIPSS). By adopting ad hoc statistical analyses, we compared survival from diagnosis of 100 PMF patients receiving ruxolitinib within COMFORT-2 with that of 350 patients of the DIPSS study. Subjects were properly matched, and both left-truncation and right-censoring were accounted in order to compare higher IPSS risks exclusively. Patients receiving ruxolitinib had longer survival (5 years, 95% confidence interval [CI]: 2.9-7.8 vs 3.5 years, 95% CI: 3.0-3.9) with a hazard ratio of 0.61 (95% CI: 0.41-0.91; P = .0148). This observation suggests that ruxolitinib may modify the natural history of PMF.

• Authors: Francesco Passamonti, Margherita Maffioli, Francisco Cervantes, Alessandro Maria Vannucchi, Enrica Morra, Tiziano Barbui, Domenica Caramazza, Lisa Pieri, Elisa Rumi, Heinz Gisslinger, Laurent Knoops, Jean Jaques Kiladjian, Barbara Mora, Norbert Hollaender, Cristiana Pascutto, Claire Harrison, Mario Cazzola
• Journal: Blood (Blood) Vol. 123 Issue 12 Pg. 1833-5 (Mar 20 2014) ISSN: 1528-0020 [Electronic] United States
• PMID: 24443442 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Nitriles
• Protein Kinase Inhibitors
• Pyrazoles
• Pyrimidines
• ruxolitinib
• Janus Kinases

Topics

• Adult
• Aged
• Aged, 80 and over
• Cohort Studies
• Female
• Humans
• Janus Kinases (antagonists & inhibitors)
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Nitriles
• Primary Myelofibrosis (drug therapy, mortality)
• Prognosis
• Protein Kinase Inhibitors (therapeutic use)
• Pyrazoles (therapeutic use)
• Pyrimidines