In-depth time-dependent analysis of the benefit of Allo-HSCT for elderly patients with CR1 AML: a FILO study

Abstract

The benefit of allogeneic hematopoietic stem cell transplantation (Allo-HSCT) for acute myeloid leukemia (AML) patients over 60 years remains a matter of debate, notably when performed in first complete remission (CR1). In order to clarify this issue, the French Innovative Leukemia Organization (FILO) performed a 10-year real-world time-dependent analysis. The study enrolled patients between 60 and 70 years of age with AML in CR1 after intensive chemotherapy with intermediate (IR) or unfavorable (UR) risk according to the European LeukemiaNet (ELN)-2010. The impact of Allo-HSCT was analyzed through three models, respectively i) time-dependent Cox, ii) multistate for dynamic prediction and iii) super landmark. The study enrolled 369 (73%) IR and 138 (27%) UR AML patients, 203 of whom received an Allo-HSCT. Classical multivariate analysis showed that Allo-HSCT significantly improved relapse-free (RFS; Hazard Ratio/HR [95%CI]: 0.47 [0.35-0.62], p<0.001) and overall (OS; HR [95%CI]: 0.56 [0.42-0.76], p<0.001) survivals, independently of the ELN risk group. With the multistate model, the predicted 5-year probability for IR and UR patients to remain in CR1 without Allo-HSCT was 8% and 1%, respectively. Dynamic predictions confirmed that patients without Allo-HSCT continue to relapse over time. Finally, the super landmark model showed that Allo-HSCT significantly improved RFS (HR [95%CI]: 0.47 [0.36-0.62], p<0.001) and OS (HR [95%CI]: 0.54 [0.40-0.72], p<0.001). Allo-HSCT in CR1 is demonstrated here to significantly improve the outcome of fit older AML patients. Long-term RFS without Allo-HSCT is very low (<10%), supporting Allo-HSCT as being the best curative option for these patients.