Long-term follow-up results of nonremission relapsed/refractory DLBCL with CAR T-cell cocktail therapy alone or in combination with ASCT

Abstract Objective: Chimeric antigen receptor T-cell (CAR-T) significantly improve clinical outcomes in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). However, approximately two-thirds of patients fail to respond to or relapse after CAR T-cell therapy. We conducted two single-arm clinical trials: CD19/CD22 chimeric antigen receptor (CAR19/22) T-cell cocktail therapy alone (Trial A) and in combination with autologous stem cell transplantation (ASCT) (Trial B). This study performs a comprehensive assessment of the long-term efficacy of therapeutic approaches in matched cohorts Methods:In this study, we analyzed real-world outcomes from two single-arm trials: Trial A (CAR19/22 T-cell “Cocktail” Therapy, ChiCTR-OPN-16008526) and Trial B (ASCT plus CAR19/22 T-cell “Cocktail” Therapy, ChiCTR-OPN-16009847). From January 2018 to December 2020, a total of 124 R/R DLBCL patients with matched baseline characteristics were enrolled in this study to evaluates the long-term efficacy and safety. Propensity score matching (PSM) and inverse probability treatment weighting (IPTW) were employed to control confounders. Results: No significant toxicities were identified in two groups within 30 days. During long-term follow-up, the most common late adverse events were cytopenia and infection. Although CAR19 and CAR22 T cells demonstrated comparable kinetics and expansion in both trials (P>0.05), Trial B exhibited distinct immunophenotypic changes: reduced Treg and expanded CD8+ T cells. With a median follow-up of 43.75 months, Trial B demonstrated enhanced therapeutic outcomes, including a higher 3-month overall response rate (84.48% vs. 54.24%, P<0.001), improved best overall response (93.22% vs. 78.46%, P=0.023), prolonged progression-free survival (PFS) (median PFS: 5.68 months vs. not reaching, P<0.001) and overall survival (OS) (median OS: 27.61 months vs. not reaching, P<0.001). Multivariate analysis confirmed that sequential therapy and achieving a complete response at 3 months are independent protective factors for long-term survival. After adjusting for baseline variables using PSM and IPTW analysis, these differences remained significant. Moreover, high-risk subgroups also demonstrated sustained survival benefits. Conclusions: Long-term follow-up demonstrated that ASCT combined with CAR-T therapy exhibited improved efficacy with favorable safety profiles compared to CAR-T therapy.