Predictors of Neurotoxicity in a Large Cohort of Italian Patients Undergoing Anti‐CD19 Chimeric Antigen Receptor (CAR) T‐Cell Therapy

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

CAR T-cell therapy for solid tumours

Ascorbate Deficiency Is Associated with Severity of Cytokine Release Syndrome Following Therapy with Chimeric Antigen Receptor T-Cells

Safety and Antitumor Effects of CD19-Specific Autologous Chimeric Antigen Receptor-Modified T (CAR-T) Cells Expressing the Inducible Caspase 9 Safety Switch (iC9-CAR19 T Cells) in Adult Acute Lymphoblastic Leukemia (ALL)

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

Imaging Activated Innate Immune Myeloid Cells in Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) Following CAR T-Cell Therapy

Chimeric Antigen Receptor T Cells: Toxicity and Management Considerations

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.

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

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)

e19506 Background: Chimeric antigen receptor (CAR) T-cell immunotherapy is a revolutionary treatment modality which has gained attention for its potential in treating multiple refractory hematological malignancies. Significant toxicities associated with CAR T- cell therapy remain a major concern. Cytokine release syndrome (CRS) and Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS) are seen early on post CAR-T cell therapy. To date, the treatment of ICANS has largely been limited to supportive care and corticosteroids. More recently, some early clinical data investigated the use of Anakinra as a promising agent in prevention and treatment of severe ICANS. Methods: We analyze three cases in which Anakinra was used to treat high-grade ICANS concurrently with high dose steroids. Results: A 51-year-old woman with high grade DLBCL and secondary CNS involvement was treated with Tisagenlecleucel CAR-T therapy. On day 2, patient became altered and was diagnosed with ICANS Grade II. High dose steroids were started leading to resolution of ICANS. However, patient’s mentation worsened by day 7, progressing to ICANS Grade IV by day 8, and Anakinra 100 mg IV was added to the steroid regimen. By day 11, after 4 doses of Anakinra, patient’s neurotoxicity completely resolved. Patient achieved a PR by day 30 after CAR-T cell infusion. In the second case, a 65-year-old man with DLBCL and leptomeningeal involvement developed ICANS Grade II on day 1 after Tisagenlecleucel CAR-T therapy and was started on high dose steroids. By day 4, neurotoxicity worsened and progressed to ICANS Grade IV. On day 5 patient was transferred to ICU for a mechanical ventilation, and Anakinra 100 mg IV was added and continued daily for 7 days. By day 12, neurotoxicity improved to ICANS grade II and patient was extubated. Meanwhile, high dose steroids were tapered. His condition acutely worsened by day 19, prompting transfer to the ICU and re-initiation of Anakinra concurrently with steroids. His family decided against further escalation of care on day 22. Patient was transitioned to comfort care and died 23 days post CAR-T cell infusion. In the third case, a 65-year-old man with mantle cell lymphoma was treated with Brexucabtagene autoleucel CAR-T therapy. On day 8, patient developed ICANS Grade I which rapidly progressed to Grade IV. High dose steroids were started and ICANS improved to Grade II on Day 9. However, on Day 10 patient’s mentation again worsened and one dose of Anakinra 100mg IV was added to the steroid regimen. By day 11, ICANS completely resolved, and patient was ultimately discharged home on day 15. Patient was able to achieve interval CR by day 30 after CAR-T cell infusion. Conclusions: In the reported cases, ICANS improved following administration of Anakinra, adding support to the idea that Anakinra may be beneficial in treatment of high-grade ICANS. Future studies are needed to better understand the overall efficacy and the ideal timeline for administration.

Absolute Lymphocyte Count As a Predictor of Safety and Efficacy Post CART for Multiple Myeloma and B Cell Malignancies

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

Peripheral Blood CAR T-Cell Level Using a Clia-Validated Assay Is Prognostic for Treatment Response and Icans in Large B-Cell Lymphoma

Comparative Analysis of Mortality from Serious Adverse Events Associated with CAR-T Therapies