Outcomes of therapy-related non-core binding factor acute myeloid leukemia with venetoclax-based therapies.

Prognosis in therapy-related acute myeloid leukemia (T-AML) remains poor, but understanding outcomes with venetoclax (VEN)-based therapy is relevant. We retrospectively analyzed 317 adult patients with newly diagnosed T-AML focusing on lower intensity therapy (LIT) VEN-containing regimens. Patients with an antecedent myeloid disorder before AML diagnosis were excluded. The median age was 69 years (range 21-92); 50% evaluated patients had a complex karyotype, and 40% evaluated patients had a mutation. Composite complete response rates were higher with LIT + VEN compared to LIT (58% vs. 40%, P = 0.003) but were similar in intensive chemotherapy (IC) + VEN versus IC alone (68% vs. 61%, P = 0.59). Rates of allogeneic hematopoietic stem cell transplantation (HSCT) were higher in VEN-treated patients: 22% versus 7% in LIT + VEN and LIT, and 64% versus 39% in IC + VEN and IC, respectively. At a median follow-up of 46.4 months, the median relapse-free survival (RFS) and overall survival (OS) of the full cohort were 7.2 and 8.4 months, respectively. Among LIT + VEN-treated patients, the median RFS and OS were 8.0 and 9.0 months, respectively; in patients with ELN2024 favorable risk, the median OS was 25.4 months (1-year OS rate of 62%), compared to 9.4 months in the intermediate (-ITD and/or mutated) and 4.8 months in the adverse risk ( mutated) group. Patients with and/or mutations had 2-year OS over 60%. On multivariate analysis in LIT + VEN-treated patients, HSCT and / mutations were favorable, while / mutations were associated with inferior survival. VEN-based therapy improves outcomes in patients with T-AML, especially in those with VEN-sensitizing genomics and receiving an HSCT.