Characteristics and Survival of Secondary Acute Myeloid Leukemia From Myelodysplastic Syndromes in Older Adults: A Population Analysis.

Abstract

Background: Acute myeloid leukemia (AML) arising from myelodysplastic syndromes (MDS) is a unique subtype of secondary AML (sAML) with poor prognosis. We defined its epidemiologic profile in older adults.

Methods: Using the SEER-Medicare database, we identified MDS cases that progressed to AML between 2007 and 2017, during the era of hypomethylating agents (HMA). Established algorithms determined demographics, MDS histology, MDS risk by Simplified Myelodysplastic Syndrome Risk Score (SMMRS), comorbidity, transfusion burden, and HMA therapy. We defined overall survival (OS) after sAML, and examined factors associated with AML and mortality, including the impact of prior HMA therapy.

Results: Of 15,227 MDS patients, 12.3% developed AML. Incidence varied by MDS histology and SMMRS. Time to AML was shorter with higher SMMRS. Older age and higher comorbidity were associated with lower odds of AML. Higher SMMRS (OR = 2.5, 95CI: 2.0-3.0), transfusion dependence (OR = 2.6, 95CI: 2.1-3.2), and HMA use (OR = 4.9, 95CI: 4.4-5.5) were associated with increased transformation risk. Median OS after AML diagnosis was 3 months. OS rates at 1 and 2 years were 25% and 12%. Survival varied by antecedent MDS histology, being longest in those with ringed sideroblasts (P < .001). Older age (HR = 1.4, 95CI: 1.1-1.9) and higher SMMRS (HR = 1.8, 95CI: 1.5-2.2) were associated with risk of death. Antecedent HMA exposure was associated with longer OS (4 vs. 2 months, P < .01), with 4 or more HMA cycles associated with decreased risk of death (HR = 0.53, 95CI: 0.47-0.60).

Conclusion: Risk of sAML is significant even in lower-risk MDS histologies. Survival is poor and varies by antecedent MDS characteristics. HMA exposure association with longer survival warrants further analysis.