Comparative effectiveness of antibody-drug conjugates and targeted therapies in acute myeloid leukemia: A network meta-analysis of 15,412 patients.

Abstract

e18535 Background: Front-line AML treatment now includes antibody–drug conjugates and targeted therapies. However, relative effectiveness across fitness and molecular subgroups has not been systematically compared. We conducted a network meta-analysis to evaluate comparative outcomes among novel approaches in newly diagnosed AML. Methods: This Bayesian random effects NMA followed PRISMA 2020 and Cochrane guidelines. PubMed, Scopus, Embase and Cochrane were searched through January 2026 for randomized studies evaluating antibody–drug conjugates, FLT3 inhibitors, IDH inhibitors, BCL-2 inhibitors, and other targeted agents. OS and CR were analyzed for intensive-eligible and ineligible patients using log-hazard ratios and odds ratios with 95% credible intervals. Treatments were ranked using SUCRA. Results: Forty-five trials enrolling 15,412 patients were included. Among intensive-eligible patients, FLT3 inhibitor regimens and gemtuzumab ozogamicin ranked highest for OS (SUCRA 69–79%), with quizartinib plus chemotherapy showing most favorable estimate (HR 0.77, 95% CrI 0.58–1.01). In intensive-ineligible patients, ivosidenib plus azacitidine showed greatest OS benefit (HR 0.44, 95% CrI 0.20–0.99; SUCRA 92%), followed by venetoclax plus azacitidine (HR 0.62). Pairwise analyses confirmed OS improvement with FLT3 inhibitors, GO, and venetoclax combinations. No increase in 30-day mortality was observed. Conclusions: ADCs and targeted treatments enhance survival in newly diagnosed AML without raising early mortality. Treatment benefit varies by molecular profile and fitness, supporting individualized selection. Key OS results. Population Treatment HR (95% CrI) Intensive-eligible FLT3i+chemo 0.74 Intensive-eligible GO+chemo 0.86 Intensive-ineligible Ivo+aza 0.44 (0.20–0.99) Intensive-ineligible Ven+aza 0.62 (0.38–1.04) Maintenance FLT3i 0.53