Propensity score-matched analysis supports the survival benefits of combination chimeric antigen receptor T-cell therapy with autologous transplantation in relapsed or refractory B-cell non-Hodgkin lymphoma: Insights from a real-world study in China

Abstract Background :Chimeric antigen receptor T-cell (CAR-T) therapy has markedly improved lymphoma outcomes. However, real-world data evaluating the survival benefit of CAR-T therapy combined with autologous stem cell transplantation (ASCT) in unselected patients are still limited. Objective This study aims to assess the efficacy and survival outcomes of ASCT combined with CAR-T therapy versus CAR-T monotherapy in relapsed or refractory B-cell non-Hodgkin lymphoma (NHL). Methods This observational, retrospective study included 217 patients with NHL hospitalized at the First Affiliated Hospital of Soochow University from June 2017 to September 2023. Patients were classified into two groups based on treatment regimens: (1) ASCT combined with CAR-T therapy (ASCT+CAR-T, n = 84), and (2) CAR-T monotherapy (CAR-T alone, n = 133). Multivariable Cox regression models were used to estimate hazard ratios (HR) for death and disease progression. A 1:1 propensity score matching was utilized to control for potential confounders in this real-world study. Results: The distribution of lymphoma subtypes was as follows: diffuse large B-cell lymphoma (DLBCL) in 171 patients (78.8%), follicular lymphoma (FL) in 10 (4.6%), mantle cell lymphoma (MCL) in 10 (4.6%), Burkitt lymphoma (BL) in 15 (6.9%), high-grade B-cell lymphoma (HGBL) in 4 (1.8%), central nervous system lymphoma (CNSL) in 5 (2.3%), and other less common subtypes in 2 (0.9%).Before matching, the ASCT+CAR-T group had significantly higher objective response rates (ORRs) (86.90% vs. 72.18%, P = 0.011) and complete response (CR) rates (65.48% vs. 42.11%, P < 0.001) compared with the CAR-T group. After a median follow-up time of 36.00 months(95% CI: 31.20–40.63), overall survival (OS) was significantly improved in the ASCT+CAR-T group compared with the CAR-T group (HR = 0.548,95% CI: 0.345–0.873,log-rank P = 0.010). Progression-free survival (PFS) showed a similar advantage (HR = 0.606, 95% CI: 0.404–0.911,log-rank P = 0.015). After 1:1 propensity score matching, CR rates remained significantly higher in the ASCT+CAR-T group compared with the CAR-T group (60.29% vs. 42.65%, P = 0.040). However, the ORRs between groups (ASCT+CAR-T 83.82% vs. CAR-T 72.06%, P = 0.098) were not statistically significant. The median follow-up time was 39.97 months (95% CI: 31.17–50.40) and 35.33 months (95% CI: 30.37–42.93) in the ASCT+CAR-T group and CAR-T group, respectively. OS remained superior in the ASCT + CAR-T group compared with the CAR-T group(HR = 0.561, 95% CI: 0.327–0.964,log-rank P = 0.034). The PFS benefit also persisted (HR = 0.599, 95% CI: 0.374–0.961,log-rank P = 0.032). Conclusion:ASCT combined with CAR-T therapy is associated with improved survival and higher remission rates compared to CAR-T alone. These findings support the potential of ASCT combined with CAR-T therapy as a favorable therapeutic approach for controlling relapsed or refractory B-cell NHL.