IC vs HMA + Ven for ND AML with very high-risk cytogenetic features

Results from a retrospective, multicenter cohort study, comparing intensive chemotherapy (IC) with hypomethylating agent + venetoclax (HMA + Ven) as first-line therapy in 358 patients with newly diagnosed (ND) acute myeloid leukemia (AML) harboring very high-risk cytogenetics (vHRC) and 840 patients with AML without vHRC, were published in Blood Neoplasia by Aguirre et al. The primary endpoint was composite complete remission (cCR) rate, and the secondary endpoint was overall survival (OS).

Key data: In patients with vHRC, cCR rates were similar with IC (n = 142) vs HMA + Ven (n = 216; 54% vs 55%; p = 0.908), with complete remission (CR) and CR with partial hematologic recovery (CRh) / CR with incomplete hematologic recovery (CRi) rates of 50% and 3.8% in the IC group vs 32.9% and 21.8% in the HMA + Ven group. In the full population (N = 1,198), median OS was significantly shorter in patients with vHRC vs those without (8.1 vs 31 months; p < 0.0001). Among patients with vHRC, median OS was longer with IC vs HMA + Ven (11.0 vs 6.5 months; p < 0.0001). On multivariable analysis, older age (p = 0.0003), prior myeloid disease (p < 0.0001), TP53 mutation (p < 0.0001), and inv(3)/t(3;3) (p = 0.0002) independently predicted inferior OS, whereas allogeneic hematopoietic stem cell transplantation (allo-HSCT) improved OS (p < 0.0001).

Key learning: In AML with vHRC, HMA + Ven demonstrated comparable remission and survival outcomes to IC, representing a reasonable first-line option for older patients, those with TP53-mutated disease, and those intended for allo-HSCT.