Work

Hypomethylating agents plus venetoclax versus intensive chemotherapy in acute myeloid leukemia with chromosome 5 and 7 abnormalities

Year: 2026

Type: article

Abstract: Abnormalities in chromosomes 5 and 7 are frequently identified in acute myeloid leukemia, are particularly enriched in therapy- and myelodysplasia-related disease, and confer an adverse prognosis. Given the high risk of relapse, allogeneic stem cell transplant (allo-SCT) is typically recommended for patients achieving complete remission following induction chemotherapy. We currently lack prospective data to decide whether intensive chemotherapy (IC) or a hypomethylating agent + venetoclax (HMA+ven) is the superior frontline treatment approach for these patients. Hence, we performed a retrospective study in a large cohort of patients with acute myeloid leukemia and deletion 7 (-7) and/or deletion 5 or 5q (-5/ del5q) comparing outcomes between patients treated with IC or HMA+ven. Remission rates after IC and HMA+ven were found to be comparable (43% vs. 52%, P=0.2). When adjusting for patient and disease characteristics in multivariable analysis, treatment with IC vs. HMA+ven did not significantly impact overall survival (hazard ratio [HR]=1.02, P=0.9202), while age at diagnosis (HR=1.02, P=0.0324), prior myeloid disease (HR=1.42, P=0.0266), monosomal karyotype (HR=1.48, P=0.029), complex karyotype (HR=1.61, P=0.0156), and KRAS mutations (HR=2.21, P=0.0063) were associated with inferior survival. There was also no difference in overall survival in patients age 60-75 years by treatment strategy (7.8 vs. 6.4 months, P=0.56), motivating future randomized trials of IC versus HMA+ven in this older population to inform optimal therapy. Importantly, overall survival was significantly improved in patients undergoing allo-SCT irrespective of frontline therapy, and allo-SCT consolidation was the most important predictor of long-term survival in multivariable analysis (HR=0.36, P<0.0001).

Source: Haematologica

DOI: 10.3324/haematol.2025.288891