Conventional Therapy vs HMA or LDAC ± Venetoclax in Older Adults With AML: Systematic Review and Meta-analysis

This systematic review summarizes the evidence informing two recommendations from the updated American Society of Hematology (ASH) guidelines for the treatment of newly diagnosed acute myeloid leukemia (AML) in older adults, comparing conventional induction and post-remission therapy versus hypomethylating agents (HMA)- or low-dose cytarabine (LDAC)-based strategies, with or without venetoclax. We searched MEDLINE, Embase, and Cochrane CENTRAL through February 2024, and monitored these databases for new studies throughout November 2024. We included randomized controlled trials (RCTs) and non-randomized studies (NRS). Reviewers screened studies, extracted data, assessed risk of bias, conducted random-effects meta-analyses, and rated certainty of evidence using GRADE. We included 21 studies (3 RCTs, 18 NRS). Compared with HMA- or LDAC-based monotherapy, conventional 7+3-type remission induction therapy may reduce mortality at longest follow-up (RR 0.94; 95% CI, 0.85-1.04; low certainty), increase complete remission rates (OR 1.75; 95% CI, 1.25-2.38; high certainty), and may reduce recurrence at longest follow-up (RR 0.81; 95% CI, 0.64-1.04; low certainty). Conventional therapies probably increase most severe toxicities (moderate certainty). Compared with HMA or LDAC combined with venetoclax, very low certainty evidence suggests that conventional therapy may reduce 1-year mortality (RR 0.72; 95% CI, 0.60-0.87), increase allogeneic transplant rates (RR 2.28; 95% CI, 1.70-3.06), result in no important differences in complete remission or recurrence, and have variable effects on severe toxicities. Conventional therapy may have benefits over HMA or LDAC alone; however, compared to HMA or LDAC plus venetoclax, the evidence remains of very low certainty.