Relapse of acute myeloid leukemia with CBFB::MYH11 fusion and KIT D816V mutation after allogeneic hematopoietic stem cell transplantation is uncommon and often associated with aggressive extramedullary spread and poor outcomes, particularly when the central nervous system is involved. We report a case of a 54‑year‑old man who developed extensive paravertebral, central nervous system, and multiorgan extramedullary relapse despite donor lymphocyte infusions and high‑dose chemotherapy. Avapritinib, a selective inhibitor of mutated KIT, was initiated as single‑agent therapy and resulted in rapid neurological improvement, complete metabolic response on positron emission tomography–computed tomography, and full molecular remission in peripheral blood. Due to temporary loss of off‑label access, avapritinib was discontinued, leading to a new extramedullary and central nervous system relapse. Remarkably, rechallenge with single‑agent avapritinib again induced molecular remission in both peripheral blood and cerebrospinal fluid, along with near‑complete metabolic response across all previously involved sites. The reproducibility of the response strongly supports a direct, target‑driven antileukemic effect. This case highlights the potential of avapritinib as an effective salvage therapy for KIT‑mutated acute myeloid leukemia with extramedullary and central nervous system involvement, including relapse after transplantation. The robust and repeated responses observed in this patient underscore the rationale the potential role of avapritinib as salvage therapy and support its investigation as a component of measurable residual disease-guided or post-transplant maintenance strategies.
Frigeni et al. (Fri,) studied this question.