Hartmut Döhner, MD, Professor of Medicine and Medical Director of the Department of Hematology and Oncology, Ulm University, Germany, discusses bleximenib combination therapy for treatment of patients with acute myeloid leukemia (AML).
AML is a cancer that affects the blood and bone marrow. The signs and symptoms of AML vary but may include easy bruising, bone pain or tenderness, fatigue, fever, frequent nosebleeds, bleeding from the gums, shortness of breath, and/or weight loss. There are many potential causes of AML such as certain blood disorders, inherited syndromes, environmental exposures, and drug exposures; however, most people who develop AML have no identifiable risk factor.
Bleximenib is a potent, selective menin inhibitor with activity in NPM1-mutated (NPM1m) or KMT2A-rearranged (KMT2Ar) AML. It is currently in phase 3 development in combination with standard AML-directed therapies. Previous studies have shown a favorable safety and efficacy profile in patients with newly diagnosed NPM1m or KMT2Ar AML treated with bleximenib plus intensive chemotherapy. Updated data from a phase 1b trial testing thesafety and efficacy of bleximenib with combination treatment was recently presented at the 2025 American Society of Hematology (ASH) meeting.
The phase 1b ALE1002 (NCT05453903) clinical trial was a multicenter, dose-finding study in which patients in cohort C1 received a standard regimen of cytarabine and daunorubicin or idarubicin in combination with bleximenib. The safety analysis included 44 patients with newly diagnosed AML. The median duration of follow-up was 6.3 months.
All patients had one or more treatment-emergent adverse event, with the most common being thrombocytopenia, neutropenia, diarrhea, nausea, anemia, and febrile neutropenia. The majority of cytopenia events were grade 3/4, consistent with an intensive chemotherapy treatment regimen. The 30-day mortality was 0% and the 60-day mortality was 2.3%. There was no differentiation syndrome observed. Three treatment-emergent adverse events of QT prolongation were reported, all grade ½ and resolved without interruption to bleximenib treatment.
Among the 37 patients who achieved composite complete response, the median time from day 1 of induction to platelet count recovery was 32 days. Additionally, the median time to neutrophil count recovery was 30 days. During induction, the median relative dose intensity of bleximenib was 100%, with no required dose reductions of co-agents.
Among the 24 patients in the intention-to-treat efficacy dataset, overall response rate was 95.8%, composite complete response was 87.5%, and complete response/complete response with partial hematologic recovery was 75%. These responses were similar across mutational subtypes. Median time to complete response was 28 days, similar to median time to first response. Median duration of response was not reached. Four patients proceeded to allogenic transplant.
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