Improved Post-Transplant Outcomes over Time for Older Patients with Acute Lymphoblastic Leukemia in First Complete Remission. a Study from the EBMT Acute Leukemia Working Party

Despite the increasing use of targeted therapies, allogeneic hematopoietic cell transplantation (allo-HCT) remains an important and potentially curative treatment modality for patients with acute lymphoblastic leukemia (ALL). Patients older than 60 years historically have performed poorly. Over time, significant progress in allo-HCT has resulted in decreased non-relapse mortality (NRM) and allowed the delivery of allo-HCT to older patients. However, little information is available about the global impact of the current standard of care for older ALL patients after allo-HCT and about the predictive factors for post-transplant outcomes. To address these challenges, we assessed real-world changes over time in transplant characteristics and post-transplant outcomes in older patients with ALL (> 60 years), comparing transplants performed in 2010-2015 with those performed in 2016-2022, using a large dataset from the European Society for Blood and Marrow Transplantation registry.

We identified 832 adult patients (49% female; median age 64 years, range 60-76) with T-ALL (N=143;17%), Philadelphia positive B-cell ALL (B Ph+; N=471; 57%), Philadelphia negative B-cell ALL (B Ph-; N=218; 26%), allografted between 2010 and 2022 in CR1 from a matched sibling donor (MSD; 26%), unrelated donor (UD; 61%) or haploidentical donor (Haplo; 11%). Karnofsky score was <90 in 30%. Conditioning was reduced intensity (RIC), myeloablative (MAC) using total body irradiation (TBI) and MAC chemotherapy in 57%, 27% and 16% of patients respectively. In vivo T cell depletion (TCD), post-transplant cyclophosphamide (PTCy) and peripheral blood stem cells (PBSCs) were given to 76%, 26% and 93% of patients, respectively. Median follow up was 3 years.

We compared changes in patient and transplant characteristics over time in 280 (34%) patients transplanted in 2010-2015, and 552 (66%) patients transplanted in 2016-2022. Patients transplanted in recent years were older, more likely to have T-ALL or B Ph-, to receive a MAC-TBI conditioning and PTCy and less likely to receive TCD. The 2-year cumulative incidence of relapse (CIR) significantly decreased from 35% to 23% whereas NRM (24% and 22% respectively). The 2-year leukemia free survival (LFS) and overall survival (OS) increased over time from 42% to 55% and from 51% to 65%, respectively. Increased in LFS and OS was observed for all three types of ALL: T-ALL (LFS 34% to 54%; OS 51% to 60%), B-Ph+ (LFS 45% to 60%; OS 53% to 71%), B Ph- (LFS 37% to 49%; OS 45% to 56%). In a Cox regression multivariate analysis (MVA), LFS was positively affected by a recent year of transplant (Hazard Ratio (HR) 0.73, p=0.034), MAC-TBI (HR 0.65, p=0.018) and use of PTCy (HR 0.68, p=0.04) but was not affected by the type of ALL. Transplantation in recent years positively affected CIR (HR= 0.55 p= 0.002) and chronic and extensive chronic GVHD (HR=0.66 p=0.037 and HR=0.49, p=0.016, respectively) whereas older age negatively affected NRM (HR=0.4, p=0.014) and chronic and extensive chronic GVHD (HR=1.76 p=0.039 and HR=2.42, p=0.023, respectively).

In conclusion, in older patients with ALL, we observed an impressive improvement over time in post-transplant outcomes with decreased CIR, chronic and extensive GVHD and improved LFS. These large-scale, real-world data can serve as a benchmark for future studies in this setting and indicate that the opportunity for transplant for the fit elderly should be mandatory and no longer an option.