Impact of extranodal involvement at CAR T-cell therapy on outcomes in patients with relapsed or refractory large B-cell lymphoma—Results from a multicenter cohort study

Extranodal (EN) diffuse large B-cell lymphoma (DLBCL) has been historically associated with inferior survival outcomes compared to nodal DLBCL. However, outcomes of patients with EN DLBCL following chimeric antigen receptor T-cell (CAR-T) therapy are not well established. In this multi-center retrospective cohort study, we evaluated the outcomes of patients with EN DLBCL who underwent CAR-T in the relapsed/refractory (R/R) setting. The primary objective was overall survival (OS), while secondary objectives included progression-free survival (PFS), response rates, and toxicity rates. A total of 218 patients were included in the analysis. The most common sites of EN involvement were skin/soft tissue (25%), bone (22%), and lung (17%). Overall response rate (ORR) and complete response rate (CRR) at first post-treatment evaluation were 62% (n = 127) and 40% (n = 82), respectively. Median follow-up was 3.5 years. Median PFS and OS were 4.0 months (95% CI = 3.1-7.2) and 25.7 months (95% CI = 16.1-51.6), respectively. Cytokine release syndrome (CRS) of any grade occurred in 73% (n = 159) of patients, and 6% (n = 12) had grade ≥ 3 CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade occurred in 37% (n = 81) of patients, and 19% (n = 41) developed grade ≥ 3 ICANS. In the multivariable analysis, factors that were independently prognostic of inferior OS were 3 or more lines of therapy prior to CAR-T, bulky disease at the time of CAR-T, hepatobiliary, and pancreas involvement, while refractory disease to the most recent therapy prior to CAR-T was associated with inferior PFS. Future studies should further evaluate outcomes of CAR-T in patients with specific EN sites of involvement that appear to be associated with inferior survival such as the liver and pancreas.