Cytokine release syndrome risk model with T-cell engaging therapies.

Significant Cytokine Release Syndrome Risk Model with T-Cell Engaging Therapies

Severe Cytokine Release Syndrome Is Associated with Impaired Hematopoietic Recovery after CD19-Targeted CAR-T Cell Therapy

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.

Utilization of Investigations for Neurotoxicity in CD19 and BCMA CART Recipients

Phase I Trial of MB-CART2019.1, a Novel CD20 and CD19 Targeting Tandem Chimeric Antigen Receptor, in Patients with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

Severe Cytokine Release Syndrome Associated with Worse Outcomes in Recipients of a Haploidentical Stem Cell Transplant

Outcomes of Patients Requiring ICU Admission after CD19 Directed CAR T-Cells

11067 Background: Cytokine release syndrome (CRS) is a potentially life-threatening complication commonly seen in patients receiving chimeric antigen receptor (CAR)-T cell therapy, allogeneic stem cell transplant, or immunotherapies. This study aims to evaluate the inpatient burden outcomes of CRS leading to hospitalization in patients diagnosed with cancer. Methods: Hospitalizations for cytokine release syndrome (CRS) were identified using ICD-10 coding from the 2020 National Inpatient Sample (NIS), the largest all-payer inpatient database in the US. Only CRS patients with a co-diagnosis of cancer (identified using the Clinical Classification Software (CCS) coding) were included in this study. The underlying severity of illness index was used to verify CRS grading. Sampling weights were applied to generate nationally representative estimates. Results: In 2020, there were 4,765 hospitalizations coded with CRS. 27.2% of these admissions had a co-diagnosis of cancer (n=1,295) and were included in the final analysis. The top co-diagnoses in the patients with CRS without cancer were COVID-19 infection and sepsis. Hematologic malignancies had the highest incidence amongst cancer types (75.7%), the distribution was as follows: 29.6% with diffuse large B-cell lymphoma, 19.9% with acute lymphoblastic leukemia, 12.8% with multiple myeloma, 12.2% with acute myeloid leukemia, and 7.7% with mantle cell lymphoma. The most common procedures in oncology patients hospitalized with CRS were CAR-T cell therapy (29.3%), chemotherapy (28.6%), stem cell transplant (8.5%), or Blinatumomab bispecific antibody (5.4%). 11.4% of patients with CRS received tocilizumab. Of those that received tocilizumab, 10% were CRS grade 2, 56.7% were grade 3, 33.3% were grade 4. 51.7% of tocilizumab was given in the first 48 hours of admission. A minority of CRS patients required critical care interventions: 12.0% requiring intubation, 5.8% requiring vasopressor support, and 2.7% received dialysis. Overall, 10.4% of all oncology admissions with CRS resulted in death during hospitalization (n=135). Of these deaths, 92.6% were in the extreme severity of illness and 63.0% were CRS grade 4. Those with CRS who died during hospitalization had a significantly longer length of stay (24.6 vs 13.6 days, p<0.001). The overall median hospital charges of a CRS-related admission were $531,692. Conclusions: This study represents the inpatient burden of CRS-related admissions in patients diagnosed with cancer. CRS admissions are commonly seen in patients with hematologic malignancies, those undergoing CAR-T cell or immunotherapies (bispecific antibodies). CRS poses a significant healthcare burden, with average hospital charges being greater than 0.5 million US dollars per admission. About 1 in 10 patients with CRS died during hospitalization with higher mortality likely with severe CRS grades and longer length of stay.

Chimeric Antigen Receptor T Cells: Toxicity and Management Considerations

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

Early Cytopenias and Infections Following Chimeric Antigen Receptor T-Cell Therapy: A Single Center Experience

Retrospective Comparison of the Roles of Tocilizumab and Siltuximab in the Management of Toxicity in CAR-T Cell Therapy for Relapsed/Refractory B-NHL

e23351 Background: Chimeric Antigen Receptor T-Cell (CAR-T) Therapy has emerged as the groundbreaking therapy for hematologic malignancies. Despites its efficacy, CAR-T therapy is associated with significant cardiac or neurological side effects have been reported. However, inpatient burden in CAR-T related adverse effects has not been explored. This study aims to address the gap in current research by analyzing inpatient burden in CAR-T using National Inpatient Sample (NIS) 2022. Methods: We included patients 18 years or older in NIS 2022 and conducted a retrospective analysis. Cancer diagnoses were identified using the Clinical Classification Software (CCS) codes. Hospitalization mortality, severity, length of stay (LOS), and costs were analyzed using R. Results: Most of the patients were equal or older than 18 years for those who received CAR-T (95.61%). Multiple myeloma (MM) was the most common disease type among CAR-T patients (185/763 patients, 24.25%) followed by diffuse large B cell lymphoma (DLBCL) (70/763 patients, 9.17%) and acute lymphoblastic leukemia (ALL) (40/896 patients, 5.24%). About two thirds of CAR-T patients were males (493/763 patients, 64.61%). About six out of ten CAR-T patients developed cytokine release syndrome (CRS) (470/763 patients, 61.60%). Patients with CRS grade 2 or greater showed significantly longer median LOS than those who are without CRS (15 vs 13 days, p = 0.003). 26.08% of CAR-T patients were diagnosed with immune effector cell-associated neurotoxicity syndrome (ICANS). The median hospital costs were 2.46% higher for those who developed CRS than those who did not ($1.37 million vs $1.34 million). Grade 4 or 5 CRS caused statistically significant high mortality during hospitalizations compared to CAR-T patients without CRS grade 4 or 5 (44.44% vs 1.46%, p = 0.041). CAR-T patients who required intubation or vasopressors had a longer median LOS (intubation; 13 vs 29.5 days, p = 0.003, vasopressor; 13 vs 22 days, p = 0.048). CAR-T patients who required vasopressors during hospitalization had 29.08% of additional charges compared who did not (Median hospital charges $1.90 million vs $1.35 million). Conclusions: Inpatient burden of CAR-T was higher in patients who experienced severe side effects such as CRS or needed intubation or vasopressors during hospitalization. Further directions should focus on developing strategies to mitigate the adverse effects and improve patients’ outcomes, ultimately enhancing the safety and effectiveness of CAR-T therapy.

Tocilizumab Administration in CAR-T Cell Associated Cytokine Release Syndrome Induces Hypofibrinogenemia

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