On June 16, 2021, the FDA approved a new indication for avapritinib (Ayvakit; Blueprint Medicines) for the treatment of adults with advanced systemic mastocytosis (AdvSM), including patients with aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic neoplasm, and mast-cell leukemia. The FDA granted this indication a priority review and breakthrough therapy and orphan drug designations.
Avapritinib was previously approved by the FDA for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumor harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations.
“For advanced SM patients, the approval of avapritinib shifts the treatment paradigm toward precision therapy that targets the primary driver of mastocytosis,” said Daniel DeAngelo, MD, PhD, Chief, Division of Leukemia, Dana-Farber Cancer Institute, Boston, MA.
The new indication was based on the results of EXPLORER and PATHFINDER, 2 multicenter, single-arm, open-label clinical trials of patients with AdvSM. The primary end point was ORR. Additional end points included DOR, time to response, and changes in individual measures of mast-cell burden. A total of 53 patients received up to 200-mg daily doses of avapritinib.
The combined ORR in all evaluable patients in both studies was 57% (95% CI, 42-70), including 28% complete remissions and 28% partial remissions. The median DOR was 38.3 months (95% CI, 19-not estimable), and the median time to response was 2.1 months.
The most common (≥20%) adverse reactions 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 × 109/L.