Long-Term Outcomes After Allogeneic Hematopoietic Stem Cell Transplantation in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma: An Italian Multicenter Collaborative Study

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) use in refractory/relapsed B-cell non-Hodgkin lymphoma (R/R B-NHL) has been reduced due to the efficacy of CAR-T-cell therapy as salvage treatment. However, there remains a need for data regarding the long-term outcomes following allo-HSCT, to fully characterize this procedure as a benchmark to design further studies on the role of allogeneic stem cell transplantation. The present study was lauched to assess the long-term outcomes of R/R B-NHL patients after allo-HSCT, in a multicenter study among six Italian hematology centers. Data were collected from 285 allo-HSCT procedures performed among 281 R/R B-NHL patients, in 2000 to 2020. All patients signed informed consent for sharing data with the GITMO/EBMT Registry, and the study was approved by the Institutional Review Board of the coordinating center. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), cumulative incidence function (CIF) of disease-related death, and non-relapse mortality (NRM). The median age at transplant was 50 yr (19 to 70), with 94 (33%) female patients. Histological subsets included indolent lymphoma (123 patients; 43.3%), aggressive lymphoma (124; 43.7%), and mantle-cell lymphoma (MCL; 37; 13%). At allo-HSCT, 135 patients (47.7%) exhibited complete remission (CR), 63 (22.3%) partial response, 30 (10.6%) stable disease, and 55 (19.4%) progressing disease. Myeloablative regimens were employed in 86 procedures (30.2%). The median follow-up for surviving patients was 8.7 yr (0.3 to 22). Three-year PFS was 43.7% (95% CI 37.9 to 49.4), 9-yr PFS 39.3% (33.4 to 45.1), 3-yr OS 50.4% (44.5 to 56.1), and 9-yr OS 46.6% (40.5 to 52.5). Positive predictors of 3-yr PFS included indolent lymphoma (55.3%) versus aggressive (37.9 %) and MCL (27.0%); and CR at allo-HSCT (51.9%) vs non-CR (30.9% to 38.9%). Similar associations were observed for OS. Among patients in CR, outcomes did not significantly differ among histological subtypes. Among patients not in CR, outcomes were significantly better for indolent lymphoma (3-yr PFS: 56.6%), compared to aggressive (26.4%), and MCL (0%). Regarding transplant procedures, the subgroup receiving post-transplant cyclophosphamide-based program for GVHD prophylaxis had a significantly improved outcome. Overall, 56 patients (19.6%) died from lymphoma progression, with 1-yr and 3-yr CIF of disease-related death of 15.9% (95% CI: 11.9 to 20.5) and 18.5 (14.2 to 23.2), respectively. The latest disease recurrence occurred at 5.4 yr post-allo-HSCT. Early NRM occurred in 75 patients (12-month CIF 26.1%), and late NRM in 25 patients (5-yr CIF 31.2%; 25.9 to 36.7). At present, 95 patients (33.3%) are long-term survivors in continuous CR at 5-22 yr since transplant. Despite pronounced toxicity, allo-HSCT is effective in high-risk, R/R B-NHL, with 5-yr PFS expectancy of ∼40%, and approximately one-third of long-term survivors in CR. Patients undergoing allo-HSCT in CR exhibited the best results. Among patients not in CR, the greatest benefits were obtained in indolent lymphoma. Allo-HSCT remains a potentially curative option for R/R B-NHL patients and further investigations are warranted to define its possible use in patients unable to undergo or failing CAR-T-cell therapy and/or bispecific monoclonal antibodies.

Keywords: Allogeneic hematopoietic stem cell transplantation; B-cell lymphoma; Early and late fatal toxicity; Long-term outcome; Salvage therapies.