Midostaurin demonstrated efficacy in patients with advanced systemic mastocytosis, including those with mast cell leukemia, a study published in The New England Journal of Medicine has shown.1

Systemic mastocytosis is a rare disorder characterized by abnormal mast cell proliferation in the bone marrow or occasionally in other internal organs. Advanced systemic mastocytosis may evolve into mast cell leukemia, an extremely aggressive subtype of acute myeloid leukemia.

Because advanced systemic mastocytosis is associated with a poor prognosis and limited treatment options, researchers evaluated the efficacy and safety of the multikinase inhibitor midostaurin, as it inhibits a primary driver of mastocytosis pathogenesis, KIT D816V.

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For this open-label study, investigators enrolled 116 patients, of whom 89 had mastocytosis-related organ damage. A total of 16 patients had aggressive systemic mastocytosis, 57 had systemic mastocytosis with an associated hematologic malignancy, and 16 had mast cell leukemia.

The overall response rate was 60% (95% CI, 49-70), with 45% of patients achieving a major response, defined as complete resolution of at least 1 type of mastocytosis-related organ damage.

Researchers found that response rates were similar regardless of disease subtype, KIT mutation status, or exposure to previous therapy. Median progression-free survival and overall survival were 14.1 and 28.7 months, respectively.

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Among the subgroup of patients with mast cell leukemia, median overall survival was 9.4 months (95% CI, 7.5-not estimable)

The most common adverse events were low-grade nausea, vomiting, and diarrhea. Grade 3 or 4 neutropenia, anemia, and thrombocytopenia were observed in 24%, 41%, and 29% of patients, respectively, mostly occurring in patients with pre-existing cytopenias. More than half (56%) of patients required dose reductions due to treatment-related toxicity.        


  1. Gotlib J, Kluin-Nelemans H, George TI, et al. Efficacy and safety of midostaurin in advanced systemic mastocytosis. N Engl J Med. 2016; 374:2530-2541.