Chimeric antigen receptor T-cell therapy for high-grade B-cell lymphoma NOS

CD19 chimeric antigen receptor T-cell (CAR-T) therapy is a pivotal part of the treatment algorithm for large B-cell lymphoma (LBCL) in the second- and third-line settings based on numerous clinical trials. However, these studies included very few patients with a diagnosis of high-grade B-cell lymphoma, not otherwise specified (HGBCL-NOS) and it is unclear if outcomes are similar to those observed with more common LBCL histologies. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we identified 111 HGBCL-NOS patients who received CAR-T therapy. The cytokine release syndrome (CRS) rate was 74% (7.7% grade 3+), median onset was 4 days (1-17) and immune effector cell-associated neurotoxicity syndrome rate was 45.2% (22.6% grade 3+), median onset was 7 days (1-17). At 2 years post-CAR-T infusion, the probability of overall survival and progression-free survival were 41.6% and 28.7% respectively. The 2-year non-relapse mortality and relapse/progression were 3.1% (95% confidence interval [CI]: 0.6-7.6) and 68.1% (95% CI: 57.9-77.6) respectively. Our analysis illustrates that patients with HGBCL-NOS represent a particularly difficult group to treat, even with CAR-T therapy. We observed that one third of patients achieved a durable response; however, the overall results were less favourable, with lower overall response rate, overall survival and progression-free survival as compared to published reports on LBCL.