Substantially Improved Survival for Intermediate Risk AML: An Australian Statewide Network Experience Spanning 20 years

• Improvement in survival across 20 years for younger adults with AML, associated with enhanced risk stratification and increased transplant

• Allogeneic transplant independently predicts improved outcomes, while achieving CR/CRi from induction is a potent predictor of survival

The management of acute myeloid leukemia (AML) continues to evolve with ongoing improvements in risk stratification and the appropriate use of allogeneic transplantation. Despite such improved guidelines, evidence for an improvement in real world AML survival is often lacking. We therefore evaluated survival outcomes and management of AML in younger adults aged 65 and under across two decades (2002-2021) in an Australian state-wide health network, contrasting differences between the more recent period (2012 to 2021) with the first decade. A total of 329 patients were evaluated retrospectively using Kaplan Meier methodology and multivariate Cox proportional hazards regression. Significantly, we observed an improvement in median overall survival between 2012-2021 compared to 2002-2011 (54 vs. 22.2 months, P=0.06). This was directly related to improvement in relapse-free survival (60 vs. 21.3 months, P=0.02), and accompanying increased use of allogeneic transplant (45 vs. 28%, P=0.003). Improvements were most profound in the intermediate cytogenetic risk group (median overall survival not reached vs. 22 months, P=0.02) with significant benefit seen for patients transplanted in this group, including FLT3-ITD. Importantly, we observed a lower relapse rate in non-transplanted AML patients managed with 3 or more consolidation cycles (58%) compared to 2 or less (81%) (P=0.04). Notably, expert guidelines for transplantation were released and adopted by local hematologists just prior to this period, in 2010. Overall, our state-wide registry data provide refreshing evidence for improved outcomes in AML, principally related to increased appropriate utilization of allogeneic transplantation and more granular risk assessment.