Cardiac safety profile of bleximenib in KMT2Ar, NPM1m, or NUP98/214r acute leukemia: Analyses from cAMeLot-1 and ALE1002

Cardiac safety results from two phase I trials evaluating bleximenib as monotherapy in patients with relapsed/refractory (R/R) KMT2A-rearranged (KMT2Ar), NPM1-mutated (NPM1m), or NUP98/214-rearranged (NUP98/214r) acute leukemia (cAMeLot-1; NCT04811560) or in combination with acute myeloid leukemia (AML)-directed therapies in patients with R/R or newly diagnosed (ND) KMT2Ar, NPM1m, or NUP98/214r AML (ALE1002; NCT05453903), were presented by Marie Luise Hütter-Krönke during the European Hematology Association (EHA) 2026 Congress.

Key data: No clinically meaningful corrected QT interval (QTc) prolongation was observed with bleximenib in cAMeLot-1 (N = 141) or ALE1002 (N = 193). An exposure–response analysis in cAMeLot-1 indicated no clinically relevant effect of bleximenib on cardiac repolarization or heart rate. Grade 3 treatment-emergent QTc prolongation occurred in one patient (0.7%) in cAMeLot-1 and one patient (0.5%) in ALE1002; no dose modifications, discontinuations, or deaths due to QTc prolongation were reported in either trial.

Key learning: Bleximenib administered as monotherapy or in a combination regimen did not prolong QTc intervals in patients with R/R or ND KMT2Ar, NPM1m, or NUP98/214r acute leukemia, and no cardiac safety signal was identified. These data indicate that QTc prolongation may not be a class effect of menin inhibitors and support the use of bleximenib alongside anti-leukemic therapies in this population.