OBJECTIVES: Advanced systemic mastocytosis (AdvSM) is a rare, clonal mast cell neoplasm characterized by abnormal mast cell infiltration of organs and tissues. AdvSM is associated with shortened overall survival (OS) and poor quality of life. Patients with AdvSM have limited treatment options, and head-to-head comparisons are missing. This research compared the relative efficacy of avapritinib versus midostaurin for the treatment of AdvSM using matching-adjusted indirect comparison (MAIC) methodology.

METHODS: A systematic literature review identified four relevant single-arm trials; two investigated avapritinib (EXPLORER and PATHFINDER) and two investigated midostaurin (D2201 and A2213). Data were pooled for studies investigating the same treatment. Unanchored MAICs were performed on overall survival (OS), overall response rate (ORR), and complete remission (CR). ORR and CR were assessed by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria. Baseline characteristics considered in the matching were age, AdvSM subtype, race, ECOG Performance Status, KIT D816V mutation status, and bone marrow mast cell burden.

RESULTS: Avapritinib improved OS and increased the response odds compared with midostaurin. For OS, comparing the efficacy population of the four studies (number of patients [n] = 85 treated with avapritinib versus n = 115 with midostaurin), the MAIC HR was 0.44 (95% confidence interval [CI]: 0.25, 0.76) and the naïve HR was 0.54 (95% CI: 0.32, 0.92). For ORR, comparing the evaluable efficacy population of the avapritinib studies (n = 79) with the efficacy population in midostaurin D2201 (n = 89), the MAIC odds ratio (OR) was 4.06 (95% CI: 3.09, 5.33) and the naïve OR was 4.08 (95% CI: 2.14, 7.79). Results from the sensitivity analyses were generally consistent.

CONCLUSIONS: This research suggests for patients with AdvSM, treatment with avapritinib is associated with improved OS and ORR compared with midostaurin. Limitations of MAICs with single-arm trial data are acknowledged.