The Efficacy of Avapritinib to Treat Advanced Systemic Mastocytosis

Brenton Mar, MD, PhD, Senior Medical Director at Blueprint Medicines, discusses the recent approval of avapritinib (brand name: Ayvakit) for the treatment of adult patients with advanced systemic mastocytosis.

Systemic mastocytosis is a rare, hematologic disorder most often caused by a mutation in the KIT D816V gene. The disorder is characterized by uncontrolled mast cell proliferation and activation across multiple organ systems, resulting in chronic, severe, and often unpredictable symptoms and extensive organ damage. A minority of systemic mastocytosis patients have advanced systemic mastocytosis, which encompasses a group of high-risk systemic mastocytosis subtypes including aggressive systemic mastocytosis, systemic mastocytosis with an associated hematological neoplasm, and mast cell leukemia.

The FDA granted approval for avapritinib, oral KIT D816V inhibitor, as a treatment for advanced systemic mastocytosis based on efficacy and safety results from the phase 1 EXPLORER and phase 2 PATHFINDER clinical trials.

According to Blueprint’s press release on the approval, treatment response was evaluated using modified IWG-MRT-ECNM criteria, with assessments based on at least 12 weeks of response duration, resolution of at least one finding of non-hematologic and hematologic organ damage, and 50% or greater reductions in biomarker response, mast cell burden and serum tryptase. The overall response rate (ORR) was defined as complete remission with full or partial hematologic recovery (CR/CRh), or partial remission (PR).

Avapritinib was generally well-tolerated, and showed robust clinical activity, including complete remissions in a significant proportion of patients. The drug showed durable clinical efficacy in advanced SM patients across disease subtypes and regardless of prior therapy. In 53 evaluable patients who had a median follow-up of 11.6 months, the ORR was 57%, and the proportion of patients with CR/CRh (28%), PR (28%) and clinical improvement (15%) was in line with previously reported results. The median duration of response was 38.3 months.

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  Mastocytosis