(ChemotherapyAdvisor) – In patients with myelofibrosis, continuous treatment with oral ruxolitinib vs. best available therapy resulted in marked and durable reductions in splenomegaly and disease-related symptoms as well as improvements in role functioning and quality of life (QOL), one of two Phase 3 studies published in the March 1, 2012, issue of the New England Journal of Medicine has found.

Results of these two studies formed the basis for the recent FDA approval of ruxolitinib, a potent and selective Janus kinase (JAK) 1 and 2 inhibitor, as the first-in-class JAK inhibitor for use in intermediate-2 and high-risk myelofibrosis. Both studies “confirmed the palliative value of ruxolitinib in terms of a partial response in splenomegaly and alleviation of constitutional symptoms,” an accompanying editorial noted.

Patients with intermediate-2 or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis were randomly assigned 2:1 to receive oral ruxolitinib (n=146) or best available oral and/or parenteral therapy (or no therapy), at the investigator’s discretion (n=73).

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At week 48, 28% of patients in the ruxolitinib group had at least a 35% reduction in spleen volume, the primary outcome measure, vs. 0% in the group receiving best available therapy (P<0.001). At week 24, these corresponding percentages were 32% and 0% (P<0.001). Mean palpable spleen length had decreased by 56% with ruxolitinib at week 48 and increased by 4% with best available therapy. Median duration of response was not reached in the ruxolitinib arm; at a median follow-up of 12 months, 80% of patients were continuing to have a response.

An improvement in overall QOL measures and a reduction in symptoms associated with myelofibrosis were observed in the ruxolitinib group. The most common grade 3 or higher hematologic abnormalities observed in either group were thrombocytopenia and anemia; these were managed with dose reduction, interruption of treatment, or transfusion. Thrombocytopenia led to one patient in each group to discontinue treatment; none discontinued due to anemia. In the best available therapy arm, two cases of acute myeloid leukemia were reported.

“This randomized, Phase 3 study shows the superiority of a JAK1 and JAK2 inhibitor over the best available therapy with respect to clinically relevant end points in patients with myelofibrosis,” the investigators wrote.

(Ed. note: see “Oral Ruxolitinib Ameliorates Debilitating Myelofibrosis-Related Symptoms, Improves Overall Survival vs. Placebo,” for results of the Phase 3 placebo-controlled study.)


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