ObjectiveTo develop a novel prognostic scoring system for severe cytokine release syndrome (CRS) in patients with B-cell acute lymphoblastic leukemia (B-ALL) treated with anti-CD19 chimeric antigen receptor (CAR)-T-cell therapy, aiming to optimize risk mitigation strategies and improve clinical management.MethodsThis single-center retrospective cohort study included 125 B-ALL patients who received anti-CD19 CAR-T-cell therapy from January 2017 to October 2023. These cases were selected from a cohort of over 500 treated patients on the basis of the availability of comprehensive baseline data, documented CRS grading, and at least 3 months of follow-up. Data on patient demographics, treatment history, laboratory parameters, CAR-T-cell characteristics, safety, and efficacy endpoints were collected. CRS severity was graded according to the 2019 ASTCT consensus criteria. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with CRS severity, and a prognostic model was constructed.ResultsThe overall incidence of CRS was 67.2%, with 13.6% having grade ≥ 3 (severe) CRS. Higher baseline and post-lymphodepletion minimal residual disease (MRD) levels and neutropenia on day 7 post-infusion were significantly associated with severe CRS. Inflammatory markers (CRP, ferritin, and IL-6) and coagulation dysfunction (APTT) on day 7 post-infusion were also predictive of CRS severity. The prognostic model incorporating these factors demonstrated robust discriminatory ability, with an area under the ROC curve of 0.875.ConclusionThis study developed a novel prognostic scoring system for severe CRS in Chinese B-ALL patients receiving anti-CD19 CAR-T-cell therapy. The model integrates clinical and laboratory parameters to facilitate early identification and management of severe CRS. Further validation in larger, prospective cohorts is warranted.

To investigate the clinical characteristics of cytokine release syndrome (CRS) in children with thalassemia major (TM) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) and their prognosis. A retrospective analysis was performed for the clinical data of 280 children with TM who underwent haplo-HSCT in the Department of Hematology and Oncology, Shenzhen Children's Hospital, from January 2019 to December 2021. According to the CRS criteria, they were divided into two groups: CRS grade <3 (260 children) and CRS grade ≥3 (20 children). The children with TM were analyzed in terms of clinical characteristics of CRS after haplo-HSCT and their prognosis. There were significant differences between the two groups in neutrophil engraftment time, clinical manifestations of CRS, and the rate of use of glucocorticoids within 4 days after haplo-HSCT (P=0.012, 0.040, and <0.001 respectively). For the CRS grade <3 group, the incidence rate of acute graft-versus-host disease (aGVHD) was 9.6% within 3 months after transplantation, while no aGVHD was observed in the CRS grade ≥3 group within 3 months after transplantation, but there was no significant difference in the incidence of aGVHD between the two groups within 3 months after transplantation (P=0.146). No transplantation-related death was observed in either group within 3 months after haplo-HSCT. The children with CRS grade≥3 have an early neutrophil engraftment time, severe and diverse clinical manifestations of CRS, and a high rate of use of glucocorticoids within 4 days after haplo-HSCT. For these children, early use of low-dose glucocorticoids after transplantation may alleviate CRS response and reduce the incidence of aGVHD, thereby bringing more benefits to the children. CRS after haplo-HSCT has no significant impact on the prognosis of the children.

Background: Chimeric antigen receptor T-cell (CAR-T) therapy targeting CD-19 utilizes ex-vivo engineered T-cells to treat refractory malignancies. Widespread CAR-T adoption is limited by resource utilization and cost, and CAR-T has also been associated with adverse cardiovascular events. Limited data exist exploring the relationship between CAR-T-associated cardiovascular events and resource utilization events (RUE). Objective: To evaluate whether CAR-T-associated cardiovascular events are associated with RUE. Methods: Records of patients treated with an FDA-approved CAR-T product between 2018 and 2022 at a single institution were reviewed. Cardiovascular events post-CAR-T were defined as arrhythmia, acute coronary syndrome, stroke, cardiovascular death, new cardiomyopathy, heart failure, or pericarditis. RUE was a composite of intensive care unit (ICU) transfer, prolonged length of stay (LOS; &gt;75th cohort percentile), and unplanned 6-month readmission. Results: Of 117 patients, 30 (26%) experienced cardiovascular events over a median 16 (IQR 7-34) months follow-up. RUE occurred in 65 patients (56%): 28 (24%) ICU transfers, 23 (20%) prolonged LOS, and 48 (41%) readmissions. Those with RUE experienced subsequent higher mortality (62% vs. 21%, p≤0.001). Among patients who experienced cardiovascular events, 24 (80%) experienced RUEs. In a Cox model, cardiovascular events (HR 2.3, 95% CI 1.3-4.1) and high cancer burden (HR 2.1, 95% CI 1.3-3.5) were independently associated with increased RUE rate, after adjusting for age, Cytokine Release Syndrome grade ≥2, atrial fibrillation history, and CAR-T costimulatory domain. Conclusion: CAR-T recipients who experience cardiovascular events also experience increased resource utilization events. Further prospective studies are needed to assess whether post-CAR-T cardiovascular event management and/or pre-therapy assessment may reduce resource utilization burden.

Introduction: Idecabtagene vicleucel (Ide-Cel) and ciltacabtagene autoleucel (Cilta-cel) are novel CAR-T therapies targeting B-cell maturation antigen (BCMA) and approved for relapsed and refractory multiple myeloma (RRMM). While cardiovascular adverse events (CVAE) are relatively common with CD-19 CAR-T, the incidence of CVAE in the real-world setting for anti-BCMA CAR-T in RRMM is largely unknown. This study aims to determine the incidence of CVAE and its associated risk factors in patients treated with ide-cel and cilta-cel. Method: This single-center retrospective cohort study evaluated RRMM patients treated with ide-cel and cilta-cel from May 2021 to December 2023. We assessed baseline cardiac and oncologic characteristics and clinical outcomes post-CAR-T. Cytokine release syndrome (CRS) and immune cell-associated neurologic syndrome (ICANS) grading followed ASTCT consensus guidelines. Result: A total of 164 RRMM patients treated with ide-cel (N=109) or cilta-cel (N=55) with at least 6 months follow-up were included. The average age was 63 years, and 57% were male. Advanced RRMM stage (R-ISS III) was present in 17% with a median of 6 prior lines of therapy. CRS grade equal or greater than 2 occurred in 22%, and ICANS grade equal or greater than 3 in 6.7%. Twenty patients (12.2%) experienced CVAE, including atrial fibrillation (7.9%), non-sustained ventricular arrhythmia (3.0%), heart failure (3.7%), and cardiovascular death (0.6%). R-ISS III was associated with increased CVAE (52.9% vs. 11.5%; P=0.001). Patients with CVAE had higher baseline ferritin and CRP levels and a higher incidence of CRS grade ≥ 2 (60% vs. 16.7%; P&lt;0.001) and ICANS grade ≥ 3 (20% vs 4.9%; P=0.001). Treatment with tocilizumab, steroids, or anakinra was more common in patients with CVAE. Conclusion: CVAE occurred relatively frequently following BCMA CAR-T therapy, with high-grade CRS identified as a consistent risk factor. Most CVAEs were manageable with appropriate supportive care, including careful observation and active treatment of CRS.

Abstract BACKGROUND Lymphomatous infiltration of the peripheral nervous system (PNS), termed neurolymphomatosis, represents a distinct extranodal non-Hodgkin lymphoma variant with dismal outcome. CD19-directed chimeric antigen receptor (CD19-CAR) T-cell therapy has emerged as a safe and effective treatment for B-cell lymphomas. We aimed to assess toxicity and efficacy of CD19-CAR T-cells in neurolymphomatosis. METHODS Neurolymphomatosis treated with CD19-CAR T-cells were retrospectively identified at Massachusetts General Hospital over a six-year period. Toxicities were graded according to the ASTCT classification. Management, and response rates were recorded. RESULTS Eleven neurolymphomatosis cases, who had received a median 2 prior PNS-directed treatments (range: 1-3) before CD19-CAR T-cell exposure, were identified. Neurolymphomatosis localized to the nerve roots (8/11, 73%), plexus (5/11, 45%), peripheral (4/11, 36%) and cranial nerves (5/11, 45%). Low grade cytokine release syndrome was detected in 8/11 (73%; grade 1: N = 7; grade 2: N =1) cases. Low- and high-grade immune cell-associated neurotoxicity syndrome were recorded in 5/11 (45%; grade 1: N = 4; grade 2: N = 1) and 1/11 (9%; grade 4) patients, respectively. Seven of eleven neurolymphomatosis patients (64%) responded to CD19-CAR T-cells. Complete remissions were achieved in three cases (27%), of which two are still sustained now 9 and 46 months after CD19-CAR T-cell infusion. All radiographic responses were associated with remission of neurological symptoms. CONCLUSIONS CD19-CAR T-cell treatment was well tolerated and yielded promising efficacy in recurrent neurolymphomatosis, a difficult to treat condition with unmet medical need. Findings suggest that CD19-CAR may sufficiently penetrate the blood-nerve barrier, and toxicity and outcomes were overall similar to CAR-T cell therapy in CNS lymphoma.

Sequential Dosing of Next-Generation IMA203CD8 TCR-T-Cell Therapy Targeting PRAME in Combination with BRAF-/MEK-Inhibition in a Melanoma Patient with Progressive Disease - a Case Report

The Efficacy of Teclistamab in Multiple Myeloma Patients with Secondary Plasma Cell Leukemia

Utilization of Investigations for Neurotoxicity in CD19 and BCMA CART Recipients

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

Predictors and Characterization of Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) in Patients with Multiple Myeloma Receiving Teclistamab

Non-Western Real-World Experience of Axi-Cel CAR-T in Refractory/Relapsed B-Cell Lymphoma from a Tertiary Center in Saudi Arabia

Remote Patient Monitoring for Early Detection of Cytokine Release Syndrome in Myeloma Patients: A Comparative Study between Standard Care and Remote Monitoring

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

Clonal Hematopoiesis of Indeterminate Potential Is Associated with Decreased Inflammatory Toxicity and Increased Late Cytopenia in Patients with Multiple Myeloma and Non-Hodgkin Lymphoma Treated with Chimeric Antigen Receptor T-Cell Therapy

Real-World Management Patterns of Acute Toxicity Following Bispecific Antibody Therapy for Patients with B-Cell Lymphoma - the Geltamo (Spanish Lymphoma Group) Experience

Coagulation Biomarker Signature As a Novel Differential Diagnostic Tool for CRS/Icans and Infection Post-CAR-T Therapy

Comparable Outcomes of Point-of-Care and Commercial CD19 CAR-T Therapies: A Patient-Matched Analysis in Large B-Cell Lymphoma

Treatment with Siltuximab for Short Term Complications after Chimeric Antigen Receptor T-Cell Therapy: A Multicenter Retrospective Analysis

Cytokine Release Syndrome in Adults Undergoing Chimeric Antigen Receptor (CAR) T-Cell Therapy in the United States; A Retrospective Analysis Via the 2021 National Inpatient Sample

The Clinical Value of Prognostic Nutritional Index in CAR-T Therapy for Patients with Malignant Lymphoma