Background:

Historically Diffuse large B-cell lymphoma (DLBCL) had poor long term survival especially in relapsed/refractory settings due to limited effective therapies which was changed after the approval of revolutionary chimeric antigen receptor T-cell (CAR-T) therapy in 2017 that led to a paradigm shift in DLBCL management there by offering durable responses and prolonging survival. This study leverages a large U.S.-based cancer registry to evaluate demographic trends and survival outcomes in DLBCL patients before and after widespread CAR-T adoption, assessing its population-level impact.

Methods:

We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database, a nationally representative U.S. cancer registry. We analyzed 44,875 patients diagnosed with advanced-stage DLBCL between 2011 and 2022, utilizing the SEER November 2024 release, which includes data from 18 registries. Patients were stratified into two cohorts based on year of diagnosis: Pre-CAR-T (2011–2016; n = 20,137) and Post-CAR-T (2017–2022; n = 24,738), corresponding to the clinical implementation of CAR-T therapy. Demographic characteristics—including age (<65 vs. ≥65 years), sex, and race (White, Black, Asian or Pacific Islander)—were compared using chi-square tests. Overall survival (OS) was estimated using Kaplan–Meier analysis, and differences between groups were assessed with log-rank tests. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for age, sex, and race.

Results:

Our study included a total of 44,875 patients with advanced diffuse large B-cell lymphoma (DLBCL). 20,137 were diagnosed in the pre-CAR-T era and 24,738 in the post-CAR-T era. The proportion of patients aged <65 years was comparable between groups (39.0% vs. 38.2%, p < 0.001). Sex distribution was balanced, with females comprising 44.3% of the pre-CAR-T group and 44.0% of the post-CAR-T group (p = 0.473). Racial composition differed significantly across eras (p < 0.001): White patients made up 82.0% of the pre-CAR-T group and 80.7% of the post-CAR-T group, while Black patients comprised 9.2% and 8.8%, respectively. Median overall survival improved substantially from 46 months (95% CI: 42–50) in the Pre-CAR-T era to 61 months (95% CI: 58–65) in the Post-CAR-T era, reflecting a 15-month gain. The Post-CAR-T cohort had fewer deaths (10,084 vs. 11,962). Multivariable analysis confirmed a 9% reduction in mortality risk in the Post-CAR-T era (HR 0.91, 95% CI: 0.89–0.94, p<0.0001), independent of demographic factors.

Conclusions:

The widespread adoption of CAR-T therapy is associated with a significant 15-month improvement in median overall survival and a 9% reduction in mortality risk among DLBCL patients at the population level, highlighting its transformative impact. These findings, derived from a large, diverse cohort, strongly support the integration of CAR-T therapy into standard DLBCL treatment protocols. Limitations include lack of treatment-specific data preventing direct confirmation of CAR-T use or evaluation of toxicities (e.g., cytokine release syndrome), limiting causal inference. Additionally, unmeasured factors such as molecular subtypes and access to specialized care may have influenced observed outcomes. Nonetheless, our findings support ongoing efforts to expand CAR-T availability and integration into standard treatment pathways for DLBCL.

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2025
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