Impact of Chimeric Antigen Receptor T-Cell Therapy on Survival in Patients with Diffuse Large B-Cell Lymphoma at the Population Level in the United States

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma diagnosed in the US each year with an incidence of 7 cases per 100,000 persons per year. The 5-year relative survival (RS) in the US population was 64% between 2008-2013 (Epperla N, Cancer Med, 2020), predating the cellular therapy era. The advent of chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment landscape of DLBCL since its first US Food and Drug Administration (FDA) approval in 2017. However, little is known regarding the impact of CAR T-cell therapy on survival in patients with DLBCL at the population level. Hence, we performed a population-based cohort study using Surveillance, Epidemiology, and End Results-17 (SEER-17) database.

Method: We included patients aged 18 years or older with pathologically confirmed DLBCL diagnosed in US between 2014-2021. Patients who were diagnosed by autopsy or death certificate or who had primary central nervous system lymphoma were excluded. The data source was the SEER-17 database that represents 27% of the US population. The study outcomes were RS and overall survival (OS). The primary exposure was period of diagnosis (2014-2017 vs 2018-2021). The periods were selected based on the first FDA-approval of CAR T-cell therapy for DLBCL. We tested the hypothesis that RS was significantly higher following the approval of CAR-T cell therapy using a multivariable flexible parametric survival model with 5 degrees of freedom for the baseline log cumulative hazard. The covariates were age at diagnosis, sex, race, stage, and presence of B symptoms. P-values < 0.05 were considered significant. Analyses were performed using STATA version 18.0.

Results: There were 51,608 patients included in the study (24,866 between 2014-2017 and 26,742 between 2018-2021). Baseline characteristics including age, sex, race, stage, and presence of B symptoms were similar between time periods. The median age at diagnosis was 68 years (interquartile range (IQR), 57-77 y). Most patients were White (n=42,207, 82%) and had advanced stage at diagnosis (n=28,216, n=55%). Median follow-up was 5.75 years (95% confidence interval (CI), 5.75-5.83) and 1.83 years (95% CI, 1.83-1.92) for patients diagnosed between 2014-2017 and 2018-2021, respectively. The corresponding 5-year RS was 64% (95% CI, 64-65%) and 66% (95% CI, 65-67%) (unadjusted HR, 0.97; 95% CI, 0.94-1.01; P=0.12). The 5-year OS increased from 54% (95% CI, 53-54%) to 55% (95% 54-56%). The estimated median OS increased from 6.78 years (95% CI, 6.44-7.13) to 7.35 years (95% CI, 6.60-8.10). On multivariable analysis, the RS for patients diagnosed between 2018-2021 was significantly higher compared to 2014-2017 (adjusted HR, 0.93; 95% CI, 0.90-0.97; P=0.001). In a sensitivity analysis restricted to only patients who received chemotherapy for DLBCL, the difference in RS remained statistically significant (adjusted HR 0.93; 95% CI, 0.88-0.98; P=0.003).

Conclusion: Our findings demonstrated improved survival for patients with DLBCL who were diagnosed between 2018-2021 when compared to the group diagnosed between 2014-2017. Although the survival benefit observed was small, it was measurable at the population level and corresponds to the CAR T-cell therapy approval in the US. The small improvement in survival likely reflects the limited use of CAR T-cell therapy in a subset of patients with relapsed/refractory disease. Future analyses are needed to evaluate the impact of CAR T-cell therapy as more patients receive the treatment earlier in their disease course.