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

Abstract

Background: 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 benchmark to design further studies on the role of allogeneic stem cell transplantation OBJECTIVE: To assess long-term outcomes of R/R B-NHL patients after allo-HSCT, in a multicenter study among six Italian hematology centers STUDY DESIGN: Data were collected from 285 allo-HSCT procedures performed among 281 R/R B-NHL patients, in 2000-2020. All patients signed informed consent for sharing data with the GITMO/EBMT Registry, 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 years (19-70), 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 years (0.3-22).

Results: Three-year PFS was 43.7% (95% CI 37.9-49.4), 9-year PFS 39.3% (33.4- 45.1), 3-year OS 50.4% (44.5-56.1), and 9-year OS 46.6% (40.5-52.5). Positive predictors of 3-year PFS included indolent lymphoma (55.3%) vs. aggressive (37.9 %) and MCL (27.0%); and CR at allo-HSCT (51.9%) vs non-CR (30.9-38.9%). 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-year 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-year and 3-year CIF of disease-related death of 15.9% (95% CI 11.9-20.5) and 18.5 (14.2-23.2), respectively. The latest disease recurrence occurred at 5.4 years post-allo-HSCT. Early NRM occurred in 75 patients (12-month CIF 26.1%), and late NRM in 25 patients (5-year CIF 31.2%; 25.9-36.7). At present, 95 patients (33.3%) are long survivors in continuous CR at 5-22 years since transplant.

Conclusions: Despite pronounced toxicity, allo-HSCT is effective in high-risk, R/R B-NHL, with 5-year PFS expectancy of ∼40%, and approximately one-third of long 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.