MPN-435 Overall Survival in Patients With Systemic Mastocytosis With Associated Hematologic Neoplasm Treated With Avapritinib Versus Best Available Therapy.

CONTEXT: Avapritinib, a selective KIT D816V inhibitor, was approved by the FDA and EMA (by EMA only after prior systemic therapy) for treating adults with advanced systemic mastocytosis (AdvSM) based on the single-arm phase 1 EXPLORER (NCT02561988) and phase 2 PATHFINDER (NCT03580655) studies. SM-AHN is the most common AdvSM subtype, however, there is no randomized controlled trial that compares the efficacy of avapritinib versus best available therapy (BAT) in this population.

OBJECTIVE: This study (NCT04695431) compared overall survival (OS) in patients with SM-AHN treated with avapritinib in EXPLORER and PATHFINDER versus patients treated with BAT in standard clinical practice.

DESIGN: A global, observational, retrospective chart review study was conducted at 6 sites to collect data on SM-AHN patients treated with BAT. These data were pooled with those from EXPLORER and PATHFINDER.

PATIENTS: Patients with SM-AHN receiving BAT were identified using inclusion/ exclusion criteria similar to EXPLORER and PATHFINDER and could contribute data on multiple lines of therapy (LOTs).

METHODS: OS, defined as time from avapritinib or BAT initiation to death from any cause, was descriptively analyzed using the Kaplan-Meier method. Inverse probability of treatment weighting (IPTW) was used to adjust for differences in key covariates between the treatment cohorts. OS was compared between cohorts using an IPTW-weighted Cox proportional hazards model.

RESULTS: 119 avapritinib (median age 70 years; 61% male) and 83 BAT patients (median age 71 years; 76% male) were included; 58% of avapritinib and 44% of BAT patients had received prior systemic therapy. BAT patients contributed 121 LOTs, most commonly tyrosine kinase inhibitors (60%) or cytoreductive therapies (38%). Median OS for avapritinib patients was 46.9 months (95% confidence interval [CI]: 44.9-not estimable) and 18.0 months (95% CI: 13.0-26.8) for BAT. Weighted Cox analyses showed that OS was significantly improved for patients treated with avapritinib versus BAT (hazard ratio [95% CI]: 0.42 [0.24-0.74]; P<0.001), after adjustment for key covariates.

CONCLUSIONS: The results of this observational, retrospective analysis indicate that patients with SM-AHN who were treated with avapritinib had significantly longer OS than patients treated with BAT. This study was sponsored by Blueprint Medicines Corporation.