The clinical impact of molecular ontogeny in acute myeloid leukemia (AML) was defined in patients treated with intensive chemotherapy. In a cohort of 314 newly diagnosed AML patients, we evaluated whether molecular ontogeny subgroups have differential benefit of venetoclax (VEN) added to hypomethylating agents (HMA). In secondary ontogeny (n = 115), median overall survival (OS)(14.1 vs. 6.9 months, P = 0.0054), composite complete remission (cCR 61% vs. 18%, P < 0.001) and allogeneic hematopoietic stem cell transplant (alloHCT) (24% vs. 6%, P = 0.02) rates were better in patients treated with HMA + VEN vs. HMA. In contrast, in TP53 AML(n = 111) median OS (5.7 vs. 6.1, P = 0.93), cCR (33% vs. 37%, P = 0.82) and alloHCT rates (15% vs. 8%, P = 0.38) did not differ between HMA + VEN vs. HMA. The benefit of VEN addition in the secondary group was preserved after adjustment for significant clinicopathologic variables (HR 0.59 [95% CI 0.38–0.94], P = 0.025). The OS benefit of HMA + VEN in secondary ontogeny was similar in those with vs. without splicing mutations (P = 0.92). Secondary ontogeny AML highlights a group of patients whose disease is selectively responsive to VEN added to HMA and that the addition of VEN has no clinical benefit in TP53-mutated AML.

分子个体发育对急性髓系白血病（AML）的临床影响是在接受强化化疗的患者中确定的。在 314 名新诊断的 AML 患者的队列中，我们评估了分子个体发育亚组是否对维奈托克 (VEN) 添加低甲基化药物 (HMA) 具有不同的益处。在继发性个体发育（n  = 115）、中位总生存期（OS）（14.1 vs 6.9 个月，P  = 0.0054）、复合完全缓解（cCR 61% vs 18%，P  < 0.001）和异基因造血干细胞移植（ alloHCT）（24% vs. 6%，P  = 0.02）HMA + VEN 治疗患者的发生率优于 . alloHCT）（ 24% vs. 6 %， P = 0.02 ）。 HMA。相比之下，在TP53 AML（n  = 111）中，中位 OS（5.7 vs. 6.1，P  = 0.93）、cCR（33% vs. 37%，P  = 0.82）和 alloHCT 率（15% vs. 8%，P  = 0.38）HMA + VEN 与 HMA 之间没有差异。在调整显着的临床病理变量后，第二组中添加 VEN 的益处得以保留（HR 0.59 [95% CI 0.38–0.94]，P  = 0.025）。在次生个体发育中，HMA + VEN 的 OS 益处与具有.没有剪接突变（P  = 0.92）。继发性个体发育 AML 强调了一组患者的疾病对添加到 HMA 的 VEN 有选择性反应，并且添加 VEN 对于TP53突变的 AML 没有临床益处。