Impact of Response to Bridging Therapy on Outcomes of CAR-T Therapy in Relapsed/Refractory DLBCL: A Single Center Retrospective Analysis
Authors: Thalambedu Nishanth , Fugere Brad , Vellanki Sruthi , Trikannad Anup Kumar , Gaddam Mamatha , Kumaran Muthu V. , Gentille Sanchez Cesar Giancarlo , Varma Ankur 
Published: December 2024

Background:

Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) remains a challenging clinical scenario, often requiring advanced therapies and Chimeric Antigen Receptor (CAR) T cell therapy has emerged as a promising treatment option. Most patients receive some form of tailored bridging therapy (BT) for disease control prior to CAR-T infusion. However, routine interim imaging is not performed after BT to assess the efficacy and therefore its impact on subsequent CAR-T outcomes are not fully understood. This study aims to evaluate the effectiveness of CAR-T therapy in patients who received physician choice BT prior to it and to analyze how BT response and 30-day post-CAR-T Positron Emission Tomography (PET) results influence long-term survival outcomes.

Methods:

We performed a single center retrospective analysis at the University of Arkansas Medical Center (UAMS) focusing on patients with relapsed/refractory DLBCL and received physician-chosen BT before undergoing CAR-T infusion with either Axi-cel or Liso-cel. Imaging, either PET or computerized tomography (CT) scans, was conducted on all patients after BT and before the infusion of CAR-T. Responses to BT and to CAR-T were categorized as follows: No response (NR) for those with Stable Disease (SD) or Progressive Disease (PD), and Response (R) for those with Complete Response (CR) or Partial Response (PR). We retrospectively gathered data on patient demographics, tumor characteristics, previous treatments, responses before and after CAR-T, and survival outcomes.

Results:

A total of 24 patients were analyzed. The median age at the time of CAR-T infusion was 68.2 years, with 33.3% (8/24) being female. 19 patients (79.2%) had denovo disease and 13 (54.2%) had extra nodal involvement. The median lines of treatment received prior to BT was 1.8 (Range:1-4). 3 (12.5%) had prior auto transplant. Most of the patients (83.3%) had ECOG 0-1 prior to CART. 22 of 24 patients received Axi-cel and the remaining received Liso-cel. 20 (83.3%) patients had NR to BT, while 4 (16.67%) had a R to BT. 19 (79.2%) patients had R to CAR-T at 30-day PET and 4 (20.8%) had a NR. At the time point of data collection, 1-year PFS (Progression Free Survival) and Overall Survival (OS) for the entire population were 67.8% and 69.4%, respectively. Post BT R vs NR was associated with a 1-year PFS of 66.7% vs 67.5% (Hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.11-8.01; P = .97), and a 1-year OS of 50% vs 73.3% (HR, 2.32; 95% CI, 0.44-12.05; P = .31). Grade 3 and above Cytokine Release Syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were developed in 4 (17.4%) and 8 (34.8%) patients, respectively with one death from grade 4 ICANS.

Conclusion:

Our retrospective analysis of relapsed or refractory DLBCL patients treated with physician choice BT followed by CAR-T therapy revealed most patients had no response to bridging therapy, reflecting the chemo refractory and aggressive nature of their DLBCL. Despite this, CAR-T therapy showed strong 1-year progression-free and overall survival rates, with no significant differences linked to bridging therapy response. Our results of the effect of BT are contrary to Roddie et al., Blood Adv, 2022 results (combination of patients who received axi-cel and tisa-cel) but in line with their results when they limited their analysis to patients who received axi-cel alone. Our study signifies that response to BT does not affect long term survival in patients who received axi-cel for their DLBCL. Prospective studies with a larger number of patients are needed to effectively answer this question.