Efficacy and Safety of Avapritinib in Previously Treated Patients with Advanced Systemic Mastocytosis

Advanced systemic mastocytosis (AdvSM) is a rare myeloid neoplasm, driven by KIT D816V mutation in >90% of patients. Avapritinib, a potent, highly selective inhibitor of D816V-mutant KIT, is approved for treatment of adults with AdvSM by the US Food and Drug Administration, regardless of prior therapy, and the European Medicines Agency, for patients with prior systemic therapy, based on EXPLORER (NCT02561988) and PATHFINDER (NCT03580655) clinical studies. We present latest pooled efficacy and safety analyses from patients who received ≥1 systemic therapy prior to avapritinib in EXPLORER/PATHFINDER. Overall response rate in response-evaluable patients (n=31) was 71% (95% confidence interval: 52-86%; 22/31), including 19% (6/31) with complete remission (CR)/CR with partial recovery of peripheral blood counts (CRh). Median time to response was 2.3 months; median time to CR/CRh was 7.4 months; median duration of response was not reached. Reductions ≥50% in bone marrow mast cell infiltration (89%), KIT D816V variant allele fraction (66%), serum tryptase (89%), and reductions ≥35% in spleen size (70%) occurred in most patients. With median follow up of 17.7 months, median OS was not reached. Avapritinib was effective in all AdvSM subtypes, regardless of number/type of prior therapies or somatic mutations associated with poor prognosis. Treatment-related adverse events (TRAEs) were observed in 94% of patients, most commonly grade 1 or 2; 57% had TRAEs ≥grade 3; 81% remained on treatment at 6 months. Avapritinib in adults with AdvSM who received prior systemic therapy was generally well tolerated with high response rates regardless of prior systemic therapy.