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

Abstract

Abnormalities in chromosomes 5 and 7 are frequently identified in acute myeloid leukemia (AML), 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 (CR) following induction chemotherapy. We currently lack prospective data to decide whether intensive chemotherapy (IC) versus 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 AML and deletion 7 (-7) and/or deletion 5 or 5q (-5/del5q) comparing outcomes between IC-versus HMA+ven-treated patients. 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 (MVA), treatment with IC vs HMA+ven did not significantly impact overall survival (OS) (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 OS 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, OS 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 MVA (HR 0.36, p<0.0001).