On June 16, 2021, the Food and Drug Administration approved avapritinib (Ayvakit™, Blueprint Medicines Corp.) for adult patients with advanced systemic mastocytosis (AdvSM), including patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL).
Efficacy was evaluated in EXPLORER (NCT02561988) and PATHFINDER (NCT03580655), two multi-center, single-arm, open-label clinical trials enrolling patients with AdvSM. The main efficacy outcome measure was overall response rate (ORR) per modified IWG-MRT-ECNM criteria, as adjudicated by a central committee. Additional efficacy measures were duration of response (DOR), time to response, and changes in individual measures of mast cell burden. Fifty-three patients received daily doses of avapritinib, up to 200 mg.
The ORR in all evaluable patients in both trials combined was 57% (95% CI: 42, 70) (n=53), with 28% complete remissions and 28% partial remissions. The median duration of response was 38.3 months (95% confidence interval: 19, not estimable) and the median time to response was 2.1 months.
The most common adverse reactions (incidence ≥ 20%) in patients with AdvSM were edema, diarrhea, nausea, and fatigue/asthenia.
Avapritinib is not recommended for the treatment of patients with AdvSM with platelet counts of less than 50 X 109/L.
The recommended avapritinib dose is 200 mg orally once daily for patients with AdvSM.
This application was granted priority review, breakthrough designation and orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
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