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Avapritinib versus midostaurin or cladribine in advanced systemic mastocytosis: a retrospective real-world external control study

As there are no prospective randomized studies in patients with advanced systemic mastocytosis (AdvSM), we compared clinical outcomes between patients treated with avapritinib in the Phase I EXPLORER (NCT02561988) and Phase II PATHFINDER (NCT03580655) trials (N=176) and patients treated with midosta...

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Main Authors: Reiter, Andreas (Author) , Gotlib, Jason (Author) , Álvarez-Twose, Iván (Author) , Radia, Deepti H. (Author) , Lübke, Johannes (Author) , Bobbili, Priyanka J. (Author) , Wang, Aolin (Author) , Dimitrijević, Saša (Author) , Sullivan, Erin (Author) , Schwaab, Juliana (Author) , Galinsky, Ilene A. (Author) , Perkins, Cecelia (Author) , Sperr, Wolfgang R. (Author) , Sriskandarajah, Priya (Author) , Mohan, Manasi (Author) , Badu, Teshawna (Author) , Sendhil, Selvam R. (Author) , Duh, Mei Sheng (Author) , Valent, Peter (Author) , DeAngelo, Daniel J. (Author)
Format: Article (Journal)
Language:English
Published: October 2025
In: Leukemia research
Year: 2025, Volume: 157, Pages: 1-10
ISSN:1873-5835
DOI:10.1016/j.leukres.2025.107919
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.leukres.2025.107919
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0145212625002796
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Author Notes:Andreas Reiter, Jason Gotlib, Iván Álvarez-Twose, Deepti H. Radia, Johannes Lübke, Priyanka J. Bobbili, Aolin Wang, Saša Dimitrijević, Erin Sullivan, Juliana Schwaab, Ilene A. Galinsky, Cecelia Perkins, Wolfgang R. Sperr, Priya Sriskandarajah, Manasi Mohan, Teshawna Badu, Selvam R. Sendhil, Mei Sheng Duh, Peter Valent, Daniel J. DeAngelo
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Summary:As there are no prospective randomized studies in patients with advanced systemic mastocytosis (AdvSM), we compared clinical outcomes between patients treated with avapritinib in the Phase I EXPLORER (NCT02561988) and Phase II PATHFINDER (NCT03580655) trials (N=176) and patients treated with midostaurin (N=99) or cladribine (N=49) from a global, multi-center, retrospective, chart review study. Overall survival (OS) and duration of treatment (DOT) were compared between the cohorts using inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazards models, and maximum reduction in serum tryptase levels was compared using adjusted generalized linear models. Median OS was not reached (95% confidence interval [CI]: 46.9 months, not estimable) for avapritinib, 28.6 (18.2, 44.6) months for midostaurin, and 23.4 (14.8, 40.6) months for cladribine. The avapritinib cohort had significantly longer OS compared to midostaurin (hazard ratio [HR] [95% CI]: 0.59 [0.36, 0.97]) and cladribine (0.32 [0.15, 0.67]), longer DOT (vs. midostaurin: 0.63 [0.41, 0.96]; vs. cladribine: 0.14 [0.09, 0.23]), and greater reduction in serum tryptase levels with mean difference [95% CI] vs. midostaurin of −72.8% [−101.1%, −44.6%] and vs. cladribine of −25.0% [−32.4%, −17.7%] (all p<0.05). Results were similar in treatment-naïve (1L) and previously treated (2L+) patients; there was improved OS in 1L avapritinib vs. 1L midostaurin patients (HR: 0.14 [0.05, 0.42]; p<0.001) and in 2L+avapritinib vs. 2L+cladribine patients (0.34 [0.16, 0.71]; p=0.004). Together, we show that avapritinib treatment resulted in significantly improved OS, longer DOT, and greater reduction in serum tryptase levels compared to midostaurin or cladribine in real-world clinical practice.
Item Description:Online verfügbar: 15. Juli 2025, Artikelversion: 24. Juli 2025
Gesehen am 18.11.2025
Physical Description:Online Resource
ISSN:1873-5835
DOI:10.1016/j.leukres.2025.107919

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