From R-CHOP to Revolution: How CAR T-Cells, ADCs, and Bispecific Antibodies Are Transforming DLBCL Treatment.

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

Association of Bridging Therapy Utilization with Clinical Outcomes in Patients Receiving Chimeric Antigen Receptor (CAR) T-Cell Therapy

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.

Acute Kidney Injury After the CAR-T Therapy Tisagenlecleucel

CAR T-cell therapy for solid tumours

Managing CAR T-Cell Toxicity: Impact of Steroid Prophylaxis on Toxicity and Outcomes

Autoimmune Outcomes in Patients with Concurrent Autoimmune Disease Receiving CD19 CAR T-Cell Therapy for Lymphoma

Glofitamab for Relapsed/Refractory Diffuse Large B-Cell Lymphoma

BackgroundCD19-directed Chimeric Antigen Receptor T-Cell (CAR-T) therapy has emerged as a promising and novel treatment for relapsed and refractory (r/r) B-cell malignancies. Efforts are directed towards increasing persistence of CAR-T...

Outcomes of Outpatient CD19-Targeted Chimeric Antigen Receptor T-Cell Therapy in Relapsed or Refractory B-Cell Lymphomas: A Systematic Review and Meta-Analysis

BackgroundCD19-directed chimeric antigen receptor (CAR) T-cell therapy has revolutionized cancer care for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Despite impressive responses seen with CAR T-cell treatment, nearly 30–50% of patients will relapse with very poor outcomes and the mechanism of relapse if oftentimes unknown. Next-generation sequencing (NGS) is a novel technology that can detect genomic biomarkers and provide insight into treatment resistance and cancer prognosis. This report highlights a case where NGS was able to detect the presence of the CAR T-cell construct in a patient after CAR T-cell therapy relapse.Case presentationWe present a 20-year-old, White, male patient with R/R DLBCL who was treated with CD19 CAR T-cell therapy and relapsed approximately six months after infusion. Biopsy showed CD19-negative disease. Interestingly, NGS detected the presence of the CAR T-cell construct even after the patient progressed following CAR T-cell therapy, suggesting continued persistence of the CAR T-cells.ConclusionsPrognosis of patients who relapse after CAR T-cell therapy for R/R DLBCL remains poor as mechanisms and predictors of relapse are not well understood. It is necessary to consider how novel technologies can be incorporated into the prognostication and monitoring of response to CAR T-cell therapy. In our case, the ability of NGS to distinguish the CAR T-cell product suggests that NGS may have the potential to ascertain CAR T-cell response and provide insight into the purported mechanism of relapse after CAR T-cell therapy. This report highlights a potentially new approach to monitoring patients with R/R DLBCL following CAR T-cell therapy using NGS technology.

Age defining immune effector cell associated neurotoxicity syndromes in aggressive large B cell lymphoma patients treated with axicabtagene ciloleucel.

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

Successful Development of an Outpatient Chimeric Antigen Receptor (CAR) T Cell Therapy Program

Feasibility of outpatient administration of axicabtagene ciloleucel and brexucabtagene autoleucel using telemedicine tools: The Vanderbilt experience.