Autologous hematopoietic cell transplantation (autoHCT) for T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL): an EBMT Lymphoma Working Party study

Introduction: THRLBCL is an orphan entity of large B-cell lymphomas (LBCL). It is dominated by stromal and immune components—especially T-cells and histiocytes—with similarities to nodular lymphocyte-predominant Hodgkin lymphoma. This microenvironment can produce immunomodulating molecules with therapeutic implications since recent reports suggest THRLBCL resistance to chimeric antigen receptor T-cells (CART). As CART-based therapies are challenging the role of autoHCT as second line consolidation for relapsed/refractory LBCL, we aimed to study the efficacy of autoHCT in THRLBCL in comparison with diffuse LBCL not other specified (DLBCL). Methods: Eligible for this EBMT registry analysis were adult patients who underwent a first autoHCT for THRLBCL between 2016 and 2020. These were compared to adult patients with DLBCL who received a first autoHCT during the same time period. Statistical analysis was descriptive and employed univariate and multivariate comparisons for the impact of baseline characteristics on survival endpoints. A 1:2 matching comparison was performed to better adjust for baseline differences between THRLBCL and DLBCL, respectively. Results: In total 11,151 patients (10,831 DLBCL, 320 THRLBCL) were identified. THRLBCL patients were younger (52 vs. 58 years), predominantly male (76% vs. 59%), had better performance status (ECOG 0: 97% vs. 92%) and less comorbidity (HCT-CI 0: 78% vs. 68%), and had a longer time from diagnosis to transplant (13 vs. 11 months) than DLBCL patients. In contrast, there were no significant differences regarding the proportion of patients receiving autoHCT during second-line (2L) treatment (87% vs. 82%) and sensitive disease status at autoHCT (95% vs. 92%) between THRLBCL and DLBCL, respectively. On logrank comparisons including all patients, THRLBCL was associated with a better 2-year overall survival (OS; 79% vs. 73%; p = 0.05) and progression-free survival (PFS; 72% vs. 61%) than DLBCL. However, when comparing 139 THRLBCL with 278 DLBCL patients matched for age, sex, disease status, performance status (PS), comorbidities (HCT-CI), and time from diagnosis, the outcome differences were no longer significant. Multivariate analyses adjusting for age, gender, disease status, PS, HCT-CI, and time from diagnosis identified higher age, refractory disease, >12 months from diagnosis, and poorer PS as significant risk factors for reduced OS and PFS. Of note, diagnosis THRLBCL was an independent predictor of reduced relapse risk (HR 0.73; p = 0.04). Conclusions: AutoHCT is an effective salvage therapy for relapsed/refractory THRLBCL sensitive to salvage therapy. Superior outcome of autoHCT for THRLBCL compared to DLBCL may be partly explained by more favorable baseline features of the THRLBCL group in terms of age, and PS. The 72% PFS-benchmark shown for autoHCT here has to be considered when deciding about 2L treatment strategies for THRLBCL. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Stem Cell Transplant Conflicts of interests pertinent to the abstract. S. Renders Honoraria: Gilead P. Dreger Honoraria: Novartis, Kite, BMS, Miltenyi