Impact of CAR T cell therapy product in the clinical outcome of patients with relapsed/refractory diffuse large B-cell lymphoma.

Abstract

e19002 Background : The management of relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) is associated with high morbidity and mortality. Chimeric antigen receptor (CAR) T-cell therapy against CD19 has emerged as a revolutionary treatment for r/r DLBCL. There are currently three FDA-approved CAR T-cell therapy products with two different co-stimulatory domains (CSD): axicabtagene ciloleucel (CD-28 CSD), tisagenlecleucel (4-1BB CSD), and lisocabtagene maraleucel (4-1BB CSD). CSDs mediate CAR-T anti-tumor effects while also influencing treatment-related toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Here, we report our real-world experience of CAR-T-cell products (CD28 vs. 4-1BB) in r/r DLBCL. Methods: We conducted a retrospective analysis of patients diagnosed with r/r DLBCL at our institute who received CAR-T therapy with 2 years of post-therapy follow-up. We collected data on baseline demographics, bridging therapy, lymphodepletion (LD) regimen, and specific CAR-T product used. Differences in clinical outcomes were determined between patients treated with CD28 vs. 4-1BB CAR-T cell products. Clinical endpoints included incidence and severity of CRS/ICANS, response rate, progression-free survival (PFS), and overall survival (OS). Survival functions were estimated using Kaplan-Meier estimators. Results: A total of 111 patients with r/r B-cell malignancies received CAR-T therapy at our institute between 2018 and 2023, of which 95 patients had r/r DLBCL diagnosis. The median age was 64 years. CRS occurred in 59 out of 95 patients (62.1%), with severe CRS (Grade 3 or 4) occurring in eight patients (13%). Fifty-four patients (57%) achieved a complete response (CR) after CAR-T therapy. Among the 54 patients who achieved CR, 22 died from treatment-related toxicities, including 7 deaths associated with COVID-19 infection. Moreover, 41 patients (43%) experienced disease progression post CAR-T therapy, and 95% of them (39 patients) died from r/r DLBCL. The median OS for the entire cohort was 14.8 months. Patients who experienced disease progression had a significantly shorter median OS of 5 months. No statistically significant differences were observed in PFS or OS based on time from apheresis to treatment, LD regimen used, or the CAR-T product (CD28 vs. 4-1BB). Conclusions: In our real-world experience, CAR-T cell therapy can cure approximately 30% of r/r DLBCL patients regardless of the cellular therapy product subtype utilized. Patients who progressed after CAR T-cell therapy prior to the availability of Bispecific T-cell engagers (BiTEs) had a dismal outcome, with most of them dying from lymphoma. In the absence of clinical trials or access to BiTEs-based therapy, early goals-of-care discussions and hospice should be considered for patients who progress after CAR T-cell therapy.