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Results of COMFORT-I, a Randomized Double-Blind, Phase III Trial of JAK1/JAK2 Inhibitor Ruxolitinib (INCB18424) vs Placebo for Patients with Myelofibrosis.

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Presentation on theme: "Results of COMFORT-I, a Randomized Double-Blind, Phase III Trial of JAK1/JAK2 Inhibitor Ruxolitinib (INCB18424) vs Placebo for Patients with Myelofibrosis."— Presentation transcript:

1 Results of COMFORT-I, a Randomized Double-Blind, Phase III Trial of JAK1/JAK2 Inhibitor Ruxolitinib (INCB18424) vs Placebo for Patients with Myelofibrosis Verstovsek S et al. Proc ASCO 2011;Abstract 6500.

2 Verstovsek S et al. Proc ASCO 2011;Abstract Introduction Myelofibrosis (MF) is characterized by splenomegaly, debilatating symptoms, cytopenias and shortened survival. MF manifests as primary myelofibrosis (PMF), post-essential thrombocythemia MF (PET-MF) or post-polycythemia vera MF (PPV-MF). Treatment of MF with conventional drugs provides only palliative benefits (Curr Opin Hematol 2006;13:87). The JAK2 V617F mutation is found in about 50% of patients with MF and is associated with certain clinical signs such as splenomegaly (Blood 2007;110:4030). Selective JAK1/JAK2 inhibitor ruxolitinib (INCB018424) has been shown to be effective in preclinical models of myeloproliferative neoplasms (Blood 2010;115:3109).

3 JAK2 Signaling Pathway Ruxolitinib Ligand Receptor Transcription Phosphorylation

4 COMFORT-I: A Phase III Trial of the JAK1/JAK2 Inhibitor Ruxolitinib Ruxolitinib 15 or 20 mg BID Ruxolitinib dose dependent upon starting platelet count: 15 mg BID if platelet count x 10 9 /L 20 mg BID if platelet count >200 x 10 9 /L Spleen volume measured by MRI every 12 weeks Eligibility PMF or PPV-MF or PET-MF Intermediate-2 or high risk by IWG-MRT criteria Palpable spleen 5 cm Platelet count 100 x 10 9 /L JAK2 V617F positive or negative R Placebo* * Crossover to ruxolitinib arm allowed Verstovsek S et al. Proc ASCO 2011;Abstract 6500.

5 Primary Endpoint: Patients with 35% Decrease in Spleen Volume (Week 24) With permission from Verstovsek S et al. Proc ASCO 2011;Abstract Patients discontinuing prior to week 24 or who crossed over prior to week 24 were considered nonresponders P < Odds ratio 134.4; 95% CI ( ,005) Ruxolitinib (n = 155) Placebo (n = 153) Responders (%)

6 Mean Percent Change from Baseline in Spleen Size Over Time With permission from Verstovsek S et al. Proc ASCO 2011;Abstract Spleen Volume (MRI or CT)Palpable Spleen Length Ruxolitinib Placebo Mean % Change ± SEM

7 Percent of Patients with 50% Symptom Score Decrease (Week 24) ITT With permission from Verstovsek S et al. Proc ASCO 2011;Abstract P < OR 15.28; 95% CI ( ) Ruxolitinib (n = 148) Placebo (n = 152) % of Patients Symptom score = sum of scores for itching, night sweats, bone/muscle pain, abdominal discomfort, pain under the left ribs, and early satiety

8 Overall Survival With permission from Verstovsek S et al. Proc ASCO 2011;Abstract Weeks Probability of Survival Ruxolitinib Placebo 10 (6.5) 14 (9.1) Number (%) of Events Hazard Ratio = 0.67 LogRank P value =

9 Hematology Laboratory Values (Worst Grade on Study*) Verstovsek S et al. Proc ASCO 2011;Abstract Ruxolitinib, n = 155Placebo, n = 151 Grade 3 % Grade 4 % Grade 3 % Grade 4 % Hemoglobin Platelets Neutrophils * Patients are included at their worst on-study grade regardless of whether this represents a change from their baseline. Grade 3/4 anemia and thrombocytopenia were more common in those with higher baseline grade. Discontinuation of treatment because of anemia and thrombocytopenia was rare (1 patient in each treatment group for each event).

10 Verstovsek S et al. Proc ASCO 2011;Abstract Conclusions Ruxolitinib demonstrated marked and sustained clinical benefits in spleen size. Symptomatic burden was reduced in patients treated with ruxolitinib. Thrombocytopenia and anemia were among the most common adverse events associated with ruxolitinib, though they rarely led to treatment discontinuation. The results of this study, combined with those of the COMFORT-II trial (Proc ASCO 2011;Abstract LBA6501), demonstrate that ruxolitinib may become a treatment option for patients with MF.


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