FDA Approves Avapritinib for Patients With Advanced Systemic Mastocytosis

Mast cell leukemia.

The FDA has granted approval to avapritinib (Ayvakit™, Blueprint Medicines Corporation), for patients with advanced systemic mastocytosis (AdvSM), including patients with aggressive systemic mastocytosis, systemic mastocytosis with an associated hematological neoplasm, and mast cell leukemia.

“Advanced systemic mastocytosis comprises a heterogeneous group of clonal mast cell neoplasms, primarily driven by KIT D816V,” wrote Jason Gotlib, MD, MS, hematologist at the Stanford Cancer Center, and colleagues in the abstract for the phase 1 EXPLORER (NCT02561988) trial, one of the studies on which the FDA approval was based. “As an exploratory post-hoc analysis of the phase 1 EXPLORER study of avapritinib in AdvSM, we evaluated responses lasting ≥12 weeks by both modified International Working-Group for Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis and pure pathologic response criteria.”

The FDA approval was based on the results of two clinical trials: EXPLORER (NCT02561988) and PATHFINDER (NCT03580655), two multi-center, single-arm, open-label clinical trials. Both clinical trials enrolled patients with AdvSM. The main efficacy outcome measure was overall response rate. Other efficacy measures included duration of response, time to response, and changes in individual measures of mast cell burden. A total of 53 patients received daily doses of avapritinib—up to 200 mg.

In both trials combined, the overall response rate was 57%, with 28% complete remissions and 28% partial remissions. The median duration of response was 38.3 months and the median time to response was 2.1 months.

The most common adverse reactions, occurring in at least 20% of patients, were edema, diarrhea, nausea, and fatigue/asthenia.

“Avapritinib with a starting dose of 200 mg once a day induced rapid, durable, and improving responses,” concluded Daniel J. DeAngelo, MD, PhD, Chief of the Division of Leukemia at the Dana-Farber Cancer Institute, and colleagues, in their PATHFINDER interim analysis at the American Association for Cancer Research virtual meeting in April 2021. “Avapritinib was well tolerated with few patients discontinuing treatment due to related adverse events.”

The recommended dose of avapritinib is 200mg orally once daily for patients with AdvSM. However, for patients with AdvSM who have platelet counts of less than 50 x 109/L, avapritinib is not recommended for treatment.

For More Information

DeAngelo DJ, Reiter A, Radia D, et al (2021). PATHFINDER: interim analysis of avapritinib in patients with advanced systemic mastocytosis (AdvSM). American Association for Cancer Research Virtual Annual Meeting 2021. Abstract CT023.

Gotlib J, Radia DH, George TI, et al (2020). Pure pathologic response is associated with improved overall survival in patients with advanced systemic mastocytosis receiving avapritnib in the phase I EXPLORER study. Blood, 136(suppl_1):37-38. DOI:10.1182/blood-2020-137413

Clinicaltrials.gov (2020). (EXPLORER) Study of BLU-285 in patients with advanced systemic mastocytosis (AdvSM) and relapsed or refractory myeloid malignancies. NLM identifier: NCT02561988.

Clinicaltrials.gov (2020). (PATHFINDER) Study to evaluate efficacy and safety of avapritinib (BLU-285), a selective KIT mutation-targeted tyrosine kinase inhibitor, in patients with advanced systemic mastocytosis. NLM identifier: NCT03580655.

Ayvakit™ (avapritinib) prescribing information (2021). Blueprint Medicines Corporation. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212608s007lbl.pdf

US Food & Drug Administration (2021). FDA approves avapritinib for advanced systemic mastocytosis. Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-avapritinib-advanced-systemic-mastocytosis

Image credit: Ayman Qasrawi at English Wikipedia. Licensed under Public Domain.

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