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

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Harrison, Claire N Vannucchi, Alessandro Maria Kiladjian, Jean-Jacques [UCL] Al-Ali, Haifa Kathrin Gisslinger, Heinz Knoops, Laurent [UCL] COMFORT-II Investigators

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.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2016
Language Anglais
Journal information "Leukemia" - Vol. 30, no.8, p. 1701-1707 (2016)
Peer reviewed yes
Publisher Nature Publishing Group ((United Kingdom) London)
issn 0887-6924
e-issn 1476-5551
Publication status Publié
Affiliations UCL - SSS/DDUV/GECE - Génétique cellulaire
UCL - (SLuc) Service d'hématologie
Links
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Bibliographic reference Harrison, Claire N ; Vannucchi, Alessandro Maria ; Kiladjian, Jean-Jacques ; Al-Ali, Haifa Kathrin ; Gisslinger, Heinz ; et. al. Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis.. In: Leukemia, Vol. 30, no.8, p. 1701-1707 (2016)
Permanent URL http://hdl.handle.net/2078.1/184666