AdvSM treatment landscape: Long-term outcomes from  the phase II PATHFINDER trial

Advanced systemic mastocytosis (AdvSM) is commonly driven by activating KIT mutations, most frequently KIT D816V, which promote mast cell proliferation and survival.¹ The development of KIT-targeted therapies has transformed the treatment landscape for AdvSM, with agents such as midostaurin and avapritinib now approved for the treatment of AdvSM and recommended in clinical guidelines.^2–6 

While non-targeted therapies, including cladribine and interferon-based approaches, remain important treatment options for selected patients, KIT-targeted therapies play a central role in the management of AdvSM.² Midostaurin was the first approved KIT-targeting therapy for AdvSM, establishing inhibition of KIT as an effective treatment strategy and providing clinically meaningful responses.⁷ Continued efforts to achieve deeper molecular responses, improve selectivity for KIT D816V, and optimize tolerability have driven the development of next-generation KIT inhibitors.⁸ Avapritinib is a highly potent and selective inhibitor of KIT D816V that has demonstrated deep and durable clinical responses across AdvSM subtypes in the phase I EXPLORER and phase II PATHFINDER.^1,8 Here, we provide an update on the evolving treatment landscape of AdvSM by summarizing key results from 4-year follow up of the phase II PATHFINDER study.¹ 

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