Real-World Outcomes Among Elderly Acute Myeloid Leukemia Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Medeiros Bruno C , Satram-Hoang Sacha , Hoang Khang Q. , Momin Faiyaz , Hurst Deborah , Reyes Carolina 
Published: October 2019

Abstract
Introduction: The incidence of acute myeloid leukemia (AML) increases with age, however treatment efficacy and tolerability in older patients are poor compared to younger patients. Without treatment, patients succumb to their illness within a few months of diagnosis. Further, disease relapse is inevitable in the majority of cases without additional post-remission therapy after successful induction of remission. The use of allogeneic hematopoietic stem cell transplantation (HSCT) is considered a potential cure for AML but its use is limited in older patients because of significant comorbidities and increased transplant-related morbidity and mortality. This retrospective study assessed outcomes of older AML patients treated with chemotherapy with or without HSCT.
Methods: The linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database, was utilized in this retrospective cohort analysis of 3327 first primary AML patients. Patients were diagnosed between January 1, 2000 to December 31, 2009, were >66 years, continuously enrolled in Medicare Part A and B with no HMO coverage in the year prior to diagnosis and received treatment with chemotherapy with or without HSCT. Chi-square test for categorical variables and ANOVA or t-test for continuous variables was used to compare patient characteristics between treated patients with and without HSCT. Kaplan-Meier curves and Cox proportional hazards regression assessed overall survival. Date of last follow-up was December 31, 2010.
Results: There were 276 (8%) patients who underwent HSCT therapy and 3051 (92%) who did not. HSCT patients were younger at diagnosis with mean age of 73 compared to the non-HSCT group (75 years; p<.0001). Seventy percent of HSCT patients compared to 55% of non-HSCT patients were under the age of 75 at diagnosis. HSCT patients were also more likely to be male. There were no statistical differences in comorbidity burden, poor performance indicators (PPI) or prior myelodysplastic syndrome (MDS) between both groups. The unadjusted median overall survival was higher for HSCT (9.7 months) compared to the non-HSCT group (4.7 months; log rank p=<0.0001). In multivariate survival analysis, patients who underwent HSCT had a 20% lower risk of death compared to those who did not receive HSCT (Table 1). Increasing age, male gender, increasing comorbidity score, prior MDS and PPI were significantly associated with higher risks of mortality. In a subset analysis stratified by age, the survival benefit with HSCT was only demonstrated in the younger age cohort ≤75 years old, and no difference in mortality risks were noted in the older age cohort >75 years (Table 1).
Conclusions: In this real-world analysis of elderly AML patients treated in community oncology practice, only 8% of patients receiving chemotherapy underwent subsequent HSCT therapy. Chronologic age appears to be the driving factor in receiving HSCT. HSCT therapy was associated with a 20% lower risk of death compared to patients receiving chemotherapy only and the survival benefit was more pronounced among the younger cohort, age ≤75 years with a 36% reduction in mortality risk. These findings provide further insight into disease management and provide an important context for identifying opportunities to improve the quality of treatment strategies in the real world setting.
Table 1: Multivariate Overall Survival Analysis HSCT All (N=3327) ≤ 75 (n=1857) >75 years (n=1470) HR 95% CI HR 95% CI HR 95% CI No ref ref ref Yes 0.80 0.69-0.92 0.63 0.53-0.75 1.22 0.97-1.54

Disclosures
Satram-Hoang: Genentech, Inc.: Consultancy. Hurst:Genentech, Inc.: Employment. Reyes:Genentech, Inc.: Employment.