Abstract 5429: REAL-AML: Real-world predictors of early mortality and treatment inequities in acute myeloid leukemia across a multi-institutional U.S. cohort.

Abstract Despite therapeutic advances, early mortality (<60 days) in newly diagnosed acute myeloid leukemia (AML) remains 15-25% in routine care, particularly among older and socioeconomically vulnerable patients. Randomized trials under-represent these groups, limiting generalizability. We conducted a multi-institutional, equity-focused analysis to identify modifiable determinants of early mortality and propose operational benchmarks for quality improvement.Adults (≥18 y) with newly diagnosed AML between 2016-2024 were identified from a federated, de-identified electronic-health-record network encompassing >35 U.S. health systems. Primary endpoint: 60-day mortality from diagnosis. Predictors included demographics, comorbidities, insurance type, urban/rural residence, facility type, cytogenetic risk, and receipt/timing of induction chemotherapy or hypomethylating-agent (HMA) regimens. Multilevel logistic regression with site random effects estimated adjusted odds ratios (aORs). Fairness analysis evaluated subgroup calibration by race, sex, and payer. Interrupted time-series modeling assessed 2020-2024 adoption of targeted agents (FLT3, IDH1/2 inhibitors). Only aggregate outputs were analyzed.Among 7,842 patients (median age 66; 47% female; 22% Black or Hispanic; 28% Medicaid/uninsured), overall 60-day mortality was 19.4% (95% CI 18.5-20.3). Independent predictors: age >70 y (aOR 2.43, 2.10-2.82), Medicaid/uninsured (aOR 1.54, 1.30-1.83), diagnosis at non-academic centers (aOR 1.39, 1.21-1.59), ECOG ≥2 (aOR 1.71, 1.50-1.95), and treatment initiation >5 days after diagnosis (aOR 1.46, 1.28-1.67). Adoption of targeted agents increased from 6% (2018) to 29% (2024), corresponding with a 5.1-point mortality reduction (p=0.003). Fairness analysis showed minimal calibration drift (ΔBrier <0.005) across demographic subgroups. Scenario modeling suggested that reducing treatment delays to ≤3 days could lower early mortality by ≈2.7% absolute (14% relative) nationwide.REAL-AML defines pragmatic, measurable drivers of early mortality in AML and identifies actionable levers-timely induction, equitable access to targeted agents, and improved insurance continuity-that could yield substantial survival benefit. This is the largest multi-system, equity-audited AML outcomes study to date and provides a template for real-world precision-implementation trials in hematologic malignancies. Citation Format: Randa Elzein, Safa Elzein, . REAL-AML: Real-world predictors of early mortality and treatment inequities in acute myeloid leukemia across a multi-institutional U.S. cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5429.