Real-world outcomes of autologous CD19-directed CAR T-cell therapy in relapsed/refractory large B-cell lymphoma: A single-center experience

Abstract Introduction Chimeric antigen receptor T-cell therapy (CART) has emerged as a pivotal treatment option for patients with relapsed or refractory large B-cell lymphoma (LBCL). However, real-world outcomes differ across institutions due to variations in patient demographics and clinical practices. In this study, we share our single-center experience with standard-of-care autologous CD19-directed CART, offering insights into its practical application and efficacy in a real-world setting. Method All eligible patients with LBCL who received commercially available approved autologous CD19-directed CART at Rush University Medical Center following the COVID-19 pandemic were included. Continuous variables were summarized using median and mean values, while categorical variables were presented as absolute numbers and percentages. Progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method. All statistical analyses were performed using Prism Version 10.5.0. Results Thirty consecutive patients from the Rush Lymphoid Disease CART Registry (December 2021 to June 2025) were included. Median age was 59 (20% ≥ 70 years old), with 33.3% female, 60% white, and 20% Hispanic. 90% patients had ECOG 0–1, and 76.7% had Ann Arbor stage III/IV disease. Eleven patients (36.7%) had double/triple-hit lymphoma, and eight (26.7%) were double expressors. Twenty-two patients (73.3%) received R-CHOP as first-line chemoimmunotherapy. Twenty-one patients (70%) had primary refractory or early relapsed (≤ 1 year) disease. The median number of prior lines of therapy before CART was 2 (range: 1–6), with 28 patients (93.3%) receiving CART after at least two prior lines of treatment. Two patients (6.7%) had prior anti-CD19 therapy, five (16.7%) had bendamustine exposure, and all patients received prior anti-CD20 monoclonal antibody. Six patients (20%) had prior autologous stem cell transplantation. The most commonly used CART product was axicabtagene ciloleucel (N=28, 93%). Before CART infusion, fifteen patients (50%) had either stable or progressive disease. Bridging therapy was administered to 25 patients (83.3%), with most receiving only one cycle (60%). Cytokine release syndrome (CRS) occurred in 28 patients (93.3%), predominantly grade 1 (N=8, 26.7%) or grade 2 (N=19, 63.3%), with one patient (3.3%) experiencing grade 3 CRS. The median onset of CRS was two days post-infusion, with a median duration of four days. Tocilizumab was administered in 19 patients (63.3%), with 13 (68.4%) requiring only one dose. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 12 patients (40%), with nine (75%) experiencing grade 1–2 and three (25%) grade 3–4. The median onset of ICANS was six days post-infusion. All ICANS patients received steroids, and four (33.3%) received anakinra. Two patients (6.7%) required intensive care unit care after CART. At day 30, twenty-nine patients (96.7%) were evaluated for prolonged cytopenia, with 13 (44.8%) experiencing prolonged grade 3–4 neutropenia and 12 (41.8%) prolonged grade 3–4 thrombocytopenia. In all thirty patients, including two patients not receiving efficacy evaluation, overall response rate was 83.3%, with a complete response rate of 60%. With a median follow-up of 8.6 months, median PFS was not reached, and the estimated 1-year PFS was 63.3% (95% CI, 40.9 to 79.1). Median OS was also not reached, and the estimated 1-year OS was 72.3% (95% CI 49.9 to 85.9). Conclusion Our institutional outcomes with CD19-directed CAR T-cell therapy are consistent with previously reported real-world data from leading cancer centers and pivotal studies in the United States, despite differences in patient demographics. These findings affirm the safety and efficacy of autologous CD19-directed CAR T-cell therapy in routine clinical practice at a medium-sized academic institution. Continued research with larger sample sizes and extended follow-up periods is warranted to validate these results further.