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This research assesses long-term efficacy and safety of CAR T-cell therapy and ASCT for relapsed/refractory DLBCL.

December 8, 2025

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

Key Points

This research assesses long-term efficacy and safety of CAR T-cell therapy and ASCT for relapsed/refractory DLBCL.
Conducted two single-arm clinical trials comparing CAR19/22 T-cell therapy and CAR19/22 with ASCT.
Analyzed outcomes from 124 R/R DLBCL patients enrolled from January 2018 to December 2020.
Utilized propensity score matching and inverse probability treatment weighting to control for confounders.
No significant toxicities observed within the first 30 days.
Trial B showed a higher overall response rate (84.48% vs. 54.24%, P<0.001).
Longest median overall survival in Trial B was 27.61 months compared to not reaching in Trial A.
Immunophenotypic changes: reduced Treg and expanded CD8+ T cells in the ASCT group.
Complete response at 3 months is a protective factor for long-term survival.

Abstract

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 (P0.05), 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%, P0.001), 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, P0.001) and overall survival (OS) (median OS: 27.61 months vs. not reaching, P0.001). 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.

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