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There are few treatment options for myelofibrosis, a myeloproliferative neoplasm causing splenomegaly and an array of symptoms including fatigue, weakness, abdominal pain, weight loss, itching, night sweats, and bone pain. Mean survival has been estimated at 4-7 years (Blood 2009 Mar 26;113(13):2895). Ruxolitinib, a selective inhibitor of Janus kinase 1 and 2, has been associated with clinical benefit in a previous case series of patients with myelofibrosis (N Engl J Med 2010 Sep 16;363(12):1117). Now, ruxolitinib has been evaluated in a large randomized trial with 309 adult patients with intermediate to high-risk myelofibrosis. Patients were randomized to ruxolitinib vs. placebo orally twice daily. The starting ruxolitinib dose was determined by baseline platelet count and adjusted for lack of efficacy or excess toxicity. Crossover from placebo to ruxolitinib was permitted for protocol-defined worsening of splenomegaly.
At median follow-up of 51 weeks, mortality was 8.4% for ruxolitinib vs. 15.6% for placebo (p = 0.05, NNT 14) (level 2 [mid-level] evidence). At planned analyses at 24 weeks, ruxolitinib was associated with significantly greater rates of patients with ≥ 50% reduction in total myelofibrosis-related symptoms (45.9% vs. 5.3%, p < 0.001, NNT 3), and patients with ≥ 35% reduction in spleen volume (41.9% vs. 0.7%, p < 0.001, NNT 3). The rate of crossover from the placebo to ruxolitinib was 23.4% (N Engl J Med 2012 Mar 1;366(9):799).
For more information, see the Myeloid Metaplasia with Myelofibrosis (MMM)topic in DynaMed.