Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis

Leukemia - Tập 30 Số 8 - Trang 1701-1707 - 2016
Claire Harrison1, Alessandro M. Vannucchi2, Jean‐Jacques Kiladjian3, Haifa Kathrin Al‐Ali4, Heinz Gisslinger5, Laurent Knoops6, Francisco Cervantes7, Mark M. Jones8, Kang Sun8, Mari McQuitty9, Viktoriya Stalbovskaya9, Prashanth Gopalakrishna9, Tiziano Barbui10
1Guy’s and St Thomas’ NHS Foundation Trust, Guy’s Hospital, London, UK
2Department of Experimental and Clinical Medicine, Center for Research and Innovation for Myeloproliferative Neoplasms-CRIMM, AOU Careggi, University of Florence, Florence, Italy
3Hôpital Saint-Louis et Université Paris Diderot, Paris, France
4University of Leipzig, Leipzig, Germany
5Medical University of Vienna, Vienna, Austria
6Cliniques Universitaires Saint-Luc and de Duve Institute, Université catholique de Louvain, Brussels, Belgium
7Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
8Incyte Corporation, Wilmington, DE, USA.
9Novartis Pharma, Basel, Switzerland
10Research Foundation, Ospedale Papa Giovanni XXIII, Bergamo, Italy

Tóm tắt

Abstract Ruxolitinib is a Janus kinase (JAK) (JAK1/JAK2) inhibitor that has demonstrated superiority over placebo and best available therapy (BAT) in the Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment (COMFORT) studies. COMFORT-II was a randomized (2:1), open-label phase 3 study in patients with myelofibrosis; patients randomized to BAT could crossover to ruxolitinib upon protocol-defined disease progression or after the primary end point, confounding long-term comparisons. At week 48, 28% (41/146) of patients randomized to ruxolitinib achieved ⩾35% decrease in spleen volume (primary end point) compared with no patients on BAT (P<0.001). Among the 78 patients (53.4%) in the ruxolitinib arm who achieved ⩾35% reductions in spleen volume at any time, the probability of maintaining response was 0.48 (95% confidence interval (CI), 0.35–0.60) at 5 years (median, 3.2 years). Median overall survival was not reached in the ruxolitinib arm and was 4.1 years in the BAT arm. There was a 33% reduction in risk of death with ruxolitinib compared with BAT by intent-to-treat analysis (hazard ratio (HR)=0.67; 95% CI, 0.44–1.02; P=0.06); the crossover-corrected HR was 0.44 (95% CI, 0.18–1.04; P=0.06). There was no unexpected increased incidence of adverse events with longer exposure. This final analysis showed that spleen volume reductions with ruxolitinib were maintained with continued therapy and may be associated with survival benefits.

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Leukemia

Tập 30 Số 8

1701-1707

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