Influence of HIV on outcomes in patients with diffuse large B cell lymphoma treated with CD19 targeting CAR-T cell therapy.

Acute Kidney Injury After the CAR-T Therapy Tisagenlecleucel

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

Chimeric Antigen Receptor T Cells: Toxicity and Management Considerations

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

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

CAR T-cell therapy for solid tumours

Cytokine Release Syndrome (CRS) Is Not Required for CAR-T Cell Efficacy in Aggressive Large B-NHL

Utilization of Investigations for Neurotoxicity in CD19 and BCMA CART Recipients

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

e19085 Background: Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are early complications, while late immune effector cell-associated hematotoxicity (ICAHT) is a delayed side effect of chimeric antigen receptor T-cell (CAR-T) therapy. Currently, no reliable predictive models exist to identify high-risk patients. This study investigates whether peripheral eosinophilia after CAR T-cell has any effect on risk of CRS, ICANS, ICAHT and infection. Methods: This multicenter, retrospective study used TriNetX database to analyze patients with B-cell lymphoma who had received CD19 CAR-T cell therapies—Liso-Cel, Axi-Cel, Brexu-Cel, or Tisa-Cel—and developed eosinophilia (>500/µL) within first month after CAR T-cell administration (Cohort 1) vs those who didn’t develop eosinophilia (Cohort 2).The outcomes of interest were the risk of CRS, ICANS, late ICAHT (after day 30), and risk of infection (after day 30) after CAR-T therapy administration. Cytopenia was defined by anemia (HgB < 8 g/dL), thrombocytopenia (PLT < 50 x 10 3 ) and neutropenia (ANC < 500/µL). Kaplan-Meier analysis, hazard ratio (HR), risk ratio (RR), and 95% CI were used to assess the outcomes. Results: A total of 3,304 patients were identified, with 524 in the eosinophilia cohort and 2,780 in the non-eosinophilia cohort. Propensity score matching (PSM) was performed using forty unique variables, including demographics (age, sex, ethnicity), baseline hemoglobin, WBC, and platelet count. Following PSM, there were 521 patients in each cohort. The eosinophilia group had a significantly lower risk of CRS (42% vs 62%, p < 0.001), ICANS (17% vs 24%, p = 0.002), and late ICAHT (49.9% vs 65.8%, p < 0.001). The risk of anemia (29.9% vs 38.8%, p = 0.003), neutropenia (37.4% vs 55.7%, p < 0.001), and thrombocytopenia (32.6% vs 44.9%, p < 0.001) were all significantly lower in the eosinophilia cohort. Infection-free survival probability was higher in the eosinophilia group (49% vs 44%, p = 0.03), with a numerically lower risk of bacterial, viral, and fungal infections. Overall survival was similar in both groups and was not significant (72% vs 71%, p = 0.59). Conclusions: This study suggests that absence of peripheral eosinophilia may identify patients at higher risk for CRS, ICANS and late ICAHT. The potential explanation for this could be that eosinophils act as potent immune effectors and immune modulators in the tumor microenvironment post-CAR-T cell therapy. These findings could guide decisions on monitoring and administration of alternative therapies. Further prospective clinical research is needed to assess eosinophilia as a prognostic marker in CAR-T therapy recipients. Eosinophilia & CAR T-cell outcomes. Cohort 1 Cohort 2 P value # of patient 521 521 - Survival Probability* 72% 71% 0.59 CRS 42% 62% <0.001 ICANS 17% 25% 0.002 ICAHT 50% 66% <0.001 Infection-free survival* 49% 44% 0.03 *At 1-year post CAR T-cell.

Background Chimeric antigen receptor (CAR) T-cell immunotherapy is increasingly used for refractory lymphoma but may lead to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Imaging may assist in clinical management. Associations between CRS or ICANS grade and imaging findings remain not fully established. Purpose To determine associations between imaging findings and clinical grade of CRS or ICANS, evaluate response patterns, and assess imaging use following CAR T-cell treatment. Materials and Methods Patients with refractory B-cell lymphoma who received CAR T-cell infusion between 2018 and 2020 at a single center were analyzed retrospectively. Clinical CRS or ICANS toxicity grade was assessed using American Society for Transplantation and Cellular Therapy, or ASTCT, consensus grading. Thoracic and head images (radiographs, CT scans, MRI scans) were evaluated. Associations between imaging findings and clinical CRS or ICANS grade were analyzed. Wilcoxon signed-rank and χ2 tests were used to assess associations between thoracic imaging findings, clinical CRS toxicity grade, and imaging-based response. Response to therapy was evaluated according to Deauville five-point scale criteria. Results A total of 38 patients (mean age ± standard deviation, 59 years ± 10; 23 men) who received CAR T-cell infusion were included. Of these, 24 (63% [95% CI: 48, 79]) and 11 (29% [95% CI: 14, 44]) experienced clinical grade 1 or higher CRS and ICANS, respectively. Patients with grade 2 or higher CRS were more likely to have thoracic images with abnormal findings (10 of 14 patients [71%; 95% CI: 47, 96] vs five of 24 patients [21%; 95% CI: 4, 37]; P = .002) and more likely to have imaging evidence of pleural effusions (five of 14 [36%; 95% CI: 10, 62] vs two of 24 [8.3%; 95% CI: 0, 20]; P = .04) and atelectasis (eight of 14 [57%; 95% CI: 30, 84] vs six of 24 [25%; 95% CI: 7, 43]; P = .048). Positive imaging findings were identified in three of seven patients (43%) with grade 2 or higher ICANS who underwent neuroimaging. The best treatment response included 20 of 36 patients (56% [95% CI: 39, 72]) with complete response, seven of 36 (19% [95% CI: 6, 33]) with partial response, one of 36 (2.8% [95% CI: 0, 8]) with stable disease, and eight of 36 (22% [95% CI: 8, 36]) with progressive disease. Conclusion Thoracic imaging findings, including pleural effusions and atelectasis, correlated with cytokine release syndrome grade following chimeric antigen receptor (CAR) T-cell infusion. CAR T-cell therapy yielded high response rates. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Langer in this issue.

Demographic Characteristics, Incidence and Outcomes of Cytokine Release Syndrome and Immune Effector Cell-Associated Neurotoxicity Syndrome in Patients Undergoing CAR T-Cell Therapy: An Analysis of the National Inpatient Sample (NIS) - 2021

Safety and Efficacy of CD22/ CD19 CAR-T and Auto-HSCT “Sandwich” Strategy As Consolidation Therapy for Ph Negative B Cell Acute Lymphoblastic Leukemia

Introduction: The efficacy of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed/refractory large B-cell lymphoma (LBCL) is limited by acute toxic events, most notably cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Identification of biomarkers of toxicities can allow for selection of high-risk patients and elucidate targetable mechanisms for mitigation. Previous biomarker studies have been constrained by relatively narrow panels of potential mediators and limited time points. Here, we employed NULISA, a novel ultrasensitive assay capable of simultaneously quantifying 204 inflammatory proteins from a single sample, to identify temporal proteome associations with acute toxicities in anti-CD19 CAR T-cell treated patients. Methods: Baseline and post-treatment peripheral blood samples from 80 patients with LBCL who underwent anti-CD19 CAR-T cell therapy were collected within specific time intervals. Plasma samples (n=480) were analyzed with NULISA. CRS and ICANS were graded according to ASTCT consensus criteria. Patients were grouped according to their maximum CRS and ICANS scores. Differential protein abundance across the toxicity groups was assessed using linear mixed effects models fit for each protein, including a time by toxicity group interaction. Proteins showing significant associations were subjected to pathway enrichment and network analysis. Results: Severe CRS and ICANS patient groups showed proteome upregulation beginning on day 1-2 and peaking at day 6-9, followed by extensive downregulation on day 11-16. The strongest upregulated pathway associations of severe CRS and ICANS were inflammatory response, IL-17 signaling, non-genomic action of vitamin D3, regulation of leukocyte proliferation, and cellular extravasation. Downregulated pathways included anti-microbial humoral response and TNFs binding to receptors. In addition to the previously identified inflammatory proteins IL-6, IFNγ, sIL-2Rα, CXCL8, CCL2, our analysis revealed significant association of several novel immune regulators and mediators. These included upregulated Th2 cytokines, IL-17A, IL-22, GZMB, CTLA4, IFNA1;IFNA13, and downregulated S100A12, IL-12B, CCL22, BDNF and TNFSFs, revealing exquisite temporal orchestration of lymphoid and myeloid activities during CRS and ICANS development. Conclusions: This study represents the most comprehensive characterization of immune response to CAR T-cell therapy to date. Using the novel NULISA technology, we identified new proteins and functional pathways associated with CAR T-cell-induced toxicity, implicating them as potential biomarkers. These previously unidentified factors also provide a platform to further investigate the causative immune mechanisms of acute toxicities in CAR-T cell therapy. Citation Format: Riley Kirkpatrick, Joanne Beer, Manishkumar S. Patel, Akansha Jalota, Agrima Mian, Ishara S. Ariyapala, Qinyu Hao, Wei Feng, Xiao-Jun Ma, Yuling Luo, Brian T. Hill, Neetu Gupta. Identification of novel biomarkers of immune toxicity from CAR T-cell therapy using ultrasensitive NULISA™ proteome technology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3867.

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