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

Clinical Lymphoma, Myeloma & Leukemia, 2022


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.


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.


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 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).


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.


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.


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.

View abstract


Reiter A, Gotlib J, Álvarez-Twose I, Radia D, Lübke J, Bobbili P, Wang A, Norregaard C, Dimitrijević S, Sullivan E, Louie-Gao M, Schwaab J, Galinsky I, Perkins C, Sperr W, Sriskandarajah P, Chin A, Sendhil S, Duh MS, Valent P, DeAngelo D