Conventional therapy vs HMA or LDAC with or without venetoclax in older adults with AML: systematic review and meta-analysis

ABSTRACT: This systematic review summarizes the evidence informing 2 recommendations from the updated American Society of Hematology guidelines for the treatment of newly diagnosed acute myeloid leukemia in older adults, comparing conventional induction and postremission therapy vs hypomethylating agents (HMA)- or low-dose cytarabine (LDAC)-based strategies, with or without venetoclax. We searched Ovid MEDLINE and Embase, and Cochrane CENTRAL through February 2024, and monitored these databases for new studies throughout November 2024. We included randomized controlled trials (RCTs) and nonrandomized studies (NRS). Reviewers screened studies, extracted data, assessed risk of bias, conducted random-effects meta-analyses, and rated certainty of evidence using GRADE (grading of recommendations, assessment, development, and evaluation). 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 (risk ratio [RR], 0.94; 95% confidence interval [CI], 0.85-1.04; low certainty), increase complete remission rates (odds ratio, 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 with HMA or LDAC plus venetoclax, the evidence remains of very low certainty.