Real world and Appalachian comparison of axicabtagene ciloleucel and lisocabtagene maraleucel in relapsed/refractory diffuse large B-cell lymphoma.

Real World Comparison of Axicabtagene Ciloleucel and Lisocabtagene Maraleucel in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Efficacy of Siltuximab for Chimeric Antigen Receptor T-Cell Therapy Toxicities - a Multicenter Retrospective Analysis

Recent trends in the management of relapsing/refractory diffuse large B-cell lymphoma: A systematic review of the literature

Development of Cytokine Release Syndrome Is Associated with Superior Progression-Free Survival in DLBCL Patients Receiving Axi-Cel or Liso-Cel

Chimeric Antigen Receptor T Cells: Toxicity and Management Considerations

Risk factors for cytokine release syndrome and neurotoxicity in patients receiving epcoritamab or glofitamab for large B cell lymphoma: A multi-center, retrospective, real world analysis.

Impact of Icans on Long-Term Neurocognitive Function in Patients with Diffuse Large B-Cell Lymphoma Receiving CAR T-Cell Therapy

Phase 2 Study of Anakinra to Prevent CRS and Neurotoxicity after Treatment with Lisocabtagene Maraleucel: Planned Interim Analysis

Chimeric Antigen Receptor T-Cell Therapy Associated Cerebral Glucose Hypometabolism (CART-CGHM): A Novel Cerebral Metabolic Complication

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.

Utilization of Investigations for Neurotoxicity in CD19 and BCMA CART Recipients

Impact of Neurological and Psychiatric Comorbidities on Toxicity and Outcomes of Patients with DLBCL Who Receive Axicabtagene Ciloleucel

7528 Background: The engineered T-cell products axicabtagene ciloleucel (axi-cel) and brexucabtagene autoleucel (brexu-cel) are FDA approved for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), respectively. This study investigated real-world rates of CRS and ICANS following CAR-T. Methods: This study analyzed CIBMTR data of US SUBJ receiving axi-cel or brexu-cel for any indication from Oct 2020–Dec 2021 with ≥1 follow-up visit. CRS and ICANS were graded per American Society for Transplantation and Cellular Therapy consensus guidelines. Results: 927 SUBJ (median age, 63 y; men, 65%) from 87 centers were analyzed. Most received axi-cel (76%), 83% of whom had DLBCL or transformed follicular lymphoma (tFL); 24% received brexu-cel (MCL). Most SUBJ had Ann Arbor stage III/IV (63%), no active central nervous system disease (84%), and refractory disease at CAR-T infusion (66%). Among all 589 SUBJ with DLBCL/tFL who received axi-cel, 54% achieved complete response, 17% partial response, and 6% stable disease. 89/715 SUBJ with available data received treatment for CRS prevention, mostly tocilizumab alone (80% [71/89]) or in combination (3% [3/89]). Overall, 766 SUBJ (83%) developed CRS (grade ≥3, 64 [8%]; Table). Of the 89 SUBJ who received CRS prevention treatment, 78% developed CRS, with 3% (3/89) having grade ≥3. 77% of SUBJ with CRS received CRS treatment, 97% of whom received tocilizumab (alone or in combination [eg, with corticosteroids]). Most (64%) SUBJ with grade 1 CRS received treatment, 63% of whom received tocilizumab alone. ICANS occurred in 424/876 SUBJ with ICANS data (48%; Table), of whom 205 (48%) had grade ≥3. ICANS treatment was reported and administered to 86% of SUBJ with ICANS, 92% of whom received corticosteroids. Conclusions: CRS and ICANS incidence rates were consistent with previously published literature and highlight potential burdens of CAR-T. In addition, the treatment landscape for CRS is changing; SUBJ with grade 1 CRS often received treatment. These data will inform the design of future studies aimed at preventing and treating CAR-T toxicities. [Table: see text]

An Endothelial Activation and Stress Index (EASIX) Based Predictive Model for Neurotoxicity and Cytokine Release Syndrome (CRS) after B-Cell Maturation Antigen (BCMA)-Directed Chimeric Antigen Receptor (CAR) T-Cell Therapy for Relapsed/Refractory Multiple Myeloma (RRMM)

Safety of Anti-CD-19 Chimeric Antigen Receptor T-Cell Therapy in the Older Population with Diffuse Large B Cell Lymphoma: A Meta-Analysis