Background

Three CD19-directed CAR T-cell therapies - axicabtagene ciloleucel (axi-cel), lisocabtagene maraleucel (liso-cel), and tisagenlecleucel (tisa-cel) - are FDA-approved for relapsed/refractory large B-cell lymphoma (R/R LBCL) following ≥2 prior lines of therapy or early relapse within 12 months of first-line treatment. Clinical studies have shown ORRs of 52-83% (CR 40-58%) in ≥3rd-line and 46-86% (CR 28-66%) in 2nd-line settings, with median PFS of 2.9-6.8 months (≥3rd-line) and 14.7 months (2nd-line, ZUMA-7 trial), respectively. In China, axi-cel and relma-cel (a CD19 CAR-T therapy developed based on liso-cel's technology but with a modified manufacturing process) have been approved for R/R LBCL. Previous studies suggested that combining CAR T-cell therapy with high-dose therapy/autologous stem cell transplantation (HDT/ASCT) may improve response rates and survival in R/R LBCL (Cao et al., 2021; Liu et al., 2024). However, these studies utilized investigational or compassionate-use CAR-T products. In this study, we report single-center outcomes from combining commercial CAR-T products (axi-cel and relma-cel) with HDT/ASCT for R/R LBCL.

Methods We retrospectively analyzed patients with R/R LBCL or transformed LBCL who received combination therapy of commercial CAR T-cell therapy (axi-cel or relma-cel) and HDT/ASCT from January 2022 to December 2024 at the Institute of Hematology & Blood Diseases Hospital. The conditioning regimen was determined by treating physicians, with CAR T-cell infusion administered on days +2, +3, or +4 following autologous stem cell reinfusion. This study was approved by the Institutional Review Board/Ethics Committee of the Blood Diseases Hospital, Chinese Academy of Medical Sciences.

Results A total of 15 patients received the combination therapy and were included in this study. Pathological classification identified 14 patients (93.3%) with de novo DLBCL and 1 patient (6.7%) with transformed follicular lymphoma. The median age was 52 years (range: 31-61), with 9 male patients (60.0%). Most patients (93.3%) had advanced-stage disease, including 4 (26.7%) with central nervous system involvement. The median lines of prior therapy was 2 (range, 1-3). At the time of leukapheresis, 8 patients (53.3%) exhibited refractory disease to their last-line therapy, 4 patients (26.7%) had achieved responses (3 PR, 1 CR), and 3 patients (20.0%) presented with relapsed disease. Following leukapheresis, thirteen patients (86.7%) underwent bridging therapy during CAR T-cell manufacturing. After combination HDT/ASCT with CAR T-cell therapy (axi-cel [n=6] or relma-cel [n=9]), the ORR was 93.3% (CR: 80.0%, PR: 13.3%). With a median follow-up duration of 25.1 months (data cutoff: July 26, 2025), the estimated 2-year progression-free survival and overall survival rates were 65.2% and 78.0%, respectively. Ten patients (66.7%) experienced cytokine release syndrome (all grade 1-2), while immune effector cell-associated neurotoxicity syndrome occurred in 3 patients (20.0%; grade 2 in 1 patient, grade 4 in 2 patients). No treatment-related mortality or unexpected toxicities were observed.

Conclusions The combination of axi-cel/relma-cel with HDT/ASCT demonstrates promising efficacy and acceptable safety in patients with R/R LBCL, representing a viable therapeutic option for transplantation-eligible candidates.

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2025
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