Outcomes of Chimeric Antigen Receptor (CAR) T-Cell Therapy in Patients with Large B-Cell Lymphoma (LBCL): A Single-Institution Experience

SIMPLE SUMMARY: Chimeric antigen receptor (CAR) T-cell therapies targeting CD19 have greatly improved the outcomes of many B-cell non-Hodgkin lymphomas, including relapsed/refractory large B-cell lymphoma (R/R LBCL). Nevertheless, a significant number of patients do not benefit. In this single-center retrospective study of patients with R/R LBCL, the outcomes of 66 patients are reported. We demonstrate that older and more frail patients are able to safely undergo CAR T-cell therapy but have significantly more infectious complications. We also demonstrate that ≥2 sites of extranodal involvement and ECOG at the time of CAR T-cell therapy are significant predictors of progression-free survival. Lastly, we demonstrate that the outcomes of patients who relapse after CAR T-cell therapy are poor. ABSTRACT: Chimeric antigen receptor T-cell (CAR T-cell) therapy has revolutionized the treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We describe the real-world baseline characteristics, efficacy, safety, and post-relapse outcomes of adult patients with R/R LBCL who received CAR T-cell therapy at the University of California San Diego. A total of 66 patients with LBCL were treated with tisagenlecleucel or axicabtagene ciloleucel. The median age was 59.5, and 21% were over 70 years old. Additionally, 20% of the patients had an Eastern Cooperative Oncology Group (ECOG) performance score of ≥2. Cytokine release syndrome incidence was 88%; immune effector cell-associated neurotoxicity syndrome incidence was 56%. All-grade infection occurred in 48% of patients and in 79% of patients > 70 years old. Complete response (CR) was achieved in 53% and partial response in 14%. Median progression-free survival (PFS) was 10.3 months; median overall survival (OS) was 28.4 months. Patients who relapsed post-CAR T-cell therapy had poor outcomes, with a median OS2 of 4.8 months. Upon multivariate analysis, both ECOG (HR 2.65, 95% CI: 1.30–5.41; p = 0.007) and ≥2 sites of extranodal involvement (HR 2.22, 95% CI: 1.15–4.31; p = 0.018) were significant predictors of PFS. Twenty-six patients were R/R to CAR T-cell therapy; six patients were in remission at the time of data cut off, one of whom received allogeneic transplant. Overall, older patients can safely undergo CAR T-cell therapy, despite the increased risk of all-grade infection. In our cohort, ECOG performance score and ≥2 sites of extranodal disease are significant predictors of PFS.