Comprehensive precise CAR-T bridging therapy for diffuse large B-cell lymphoma: A multicenter study from the Chinese Southwest Study Group.

Abstract

7027 Background: Chimeric antigen receptor T-cell (CAR-T) therapy has showed substantial efficacy in relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). However, over 50-60% of patients fail to respond or relapse following CAR T-cell treatment, underscoring the need for strategies to enhance its efficacy. Methods: We prospectively evaluated the efficacy of the Chinese Southwest Oncology Group (CSWOG) regimen, a precise bridging strategy, in patients with r/r DLBCL who received commercial CAR-T therapy. All patients underwent re-biopsy to assess the expression of biomarkers including CD19, CD20, CD22, CD30, CD38, CD79b, ALK, BCL2, PD-L1, and Ki-67 to identify potential treatment targets. Only patients with positive CD19 expression were eligible for inclusion. Patients received a precise salvage therapy consisting of non-cross-resistant chemotherapy and targeted immunotherapy guided by the re-biopsy results. Only those who responded to salvage therapy proceeded to leukapheresis and received an additional cycle of salvage immunochemotherapy. Non-responders were switched to an alternative precise regimen. Based on our previous findings that low-dose radiation enhances CAR-T cell recruitment and increases antigen exposure, all patients received involved-field low-dose radiation prior to CAR-T cell infusion. Patients treated with axicabtagene ciloleucel (axi-cel) in a real-world setting served as the control group. Results: Seventy-one patients with r/r DLBCL received the CSWOG bridging regimen, while 101 Chinese patients treated with axi-cel in a real-world setting served as the control group. In the CSWOG group, 63 patients (88.7%) responded to salvage precise immunochemotherapy, while 8 patients (11.3%) who did not respond were switched to alternative immunochemotherapy regimen. All patients in the CSWOG group received a median dose of 24.0 Gy involved-field radiation. After CAR-T infusion, the best overall response (BOR) rate was 84.5% in CSWOG group, with 74.6% achieving complete response (CR) and 9.9% partial response (PR). The BOR rate in control group was 83.2%, with 58.4% achieving CR and 24.8% achieving PR. After a median follow-up of 15.3 months, the 2 - year overall survival (OS) and progression-free survival (PFS) rates were 84.1% and 75.2%, respectively, in the CSWOG group, compared to 70.0% and 49.8% in the control group. Grade 3 or higher cytokine release syndrome occurred in 9.8% of the CSWOG group and 15.2% of the control group. Neurologic events of any grade were observed in 12.8% of the CSWOG group and 16.2% of the control group. Among the 4 CSWOG patients with neurologic events, all were managed with steroids and resolved; however, all 4 relapsed. Conclusions: Our results show that combining precise immunochemotherapy with low-dose radiation optimizes CAR-T therapy, supporting its global implementation. Clinical trial information: ChiCTR2100043613 .