Abstract 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 TP53 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 ( FLT3 ‐ITD and/or RAS mutated) and 4.8 months in the adverse risk ( TP53 mutated) group. Patients with NPM1 and/or IDH mutations had 2‐year OS over 60%. On multivariate analysis in LIT + VEN‐treated patients, HSCT and NPM1 / IDH2 mutations were favorable, while TP53 / RAS 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.
Carter et al. (Sun,) studied this question.