Regional hypometabolism on brain FDG-PET one month after receiving chimeric antigen receptor T-cell therapy may be associated with icans

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

Biomarker correlates of clinical outcomes from a global Phase 1b study of JNJ-90014496, CD20/CD19 bi-specific chimeric antigen receptor (CAR) T-cell therapy for patients with large B-cell lymphoma (LBCL)

Real World Experience with a Zuma -1 Cohort 4 Adopted Approach to CRS and Icans in CAR-T Recipients

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

Impact of Pre-Existing Mental Health Disorders (MHD) on CAR T-Cell Therapy Outcomes in Patients with Large B-Cell Lymphoma

<h3>Background and Importance</h3> Chimeric Antigen Receptor T-cell (CAR-T) therapy has improved outcomes in relapsed or refractory haematological malignancies. Nevertheless, immune effector cell-associated neurotoxicity syndrome (ICANS) is a relevant complication, frequently associated with cytokine release syndrome (CRS), and may lead to intensive care unit (ICU) admission or death. <h3>Aim and Objectives</h3> To describe the incidence, characteristics, and outcomes of ICANS in patients treated with CAR-T therapy, focusing on the most prevalent diagnoses and products. <h3>Material and Methods</h3> Observational, retrospective study including all patients receiving CAR-T therapy between January 2020 and April 2025. Data were collected from electronic health records (OrionClinic). Variables: demographics, diagnosis, CAR-T product, hospital stay, CRS, ICANS (incidence, duration, relapses, treatment and response, CRS concomitance), ICU admission and ICANS-related mortality. Continuous variables were expressed as median (interquartile range, IQR), and categorical variables as absolute and relative frequencies. Statistical analysis was performed with R v.4.4.3 <h3>Results</h3> Seventy patients were included, median age 61 years (52–68), 54% men. Main diagnoses: diffuse large B-cell lymphoma (DLBCL, n = 53, 76%), acute lymphoblastic leukaemia (ALL, n = 6, 9%), and multiple myeloma (MM, n = 6, 9%). CAR-T products: axicabtagene ciloleucel (n = 37, 53%), tisagenlecleucel (n = 20, 29%) and ciltacabtagene autoleucel (n = 5, 7%), other academic or commercialised products (11%). ICANS occurred in 26 patients (37%), developing at 6.5 days (4.25–8.0) post-infusion, lasting 2 days (1–3). Grades: 10 patients (38.5%) grade 1, 3 (11.5%) grade 2, 9 (34.6%) grade 3, and 4 (15.4%) grade 4; 50% were severe (grade 3–4). CRS occurred in 60 (86%), concomitant with ICANS in 10 (14%). Relapses occurred in 9 (13%). Corticosteroids were the main treatment; anakinra was reserved for refractory cases. ICU admission due to ICANS was required in 20 (29%). Mortality directly related to ICANS was 1 case. By product, ICANS incidence was: axicabtagene ciloleucel 23/37 (62%) vs tisagenlecleucel 0%. By main diagnosis: DLBCL 23/53 (43%), ALL 1/6 (17%) and MM 0%. <h3>Conclusion and Relevance</h3> ICANS occurred in over one-third of patients, especially in DLBCL treated with axicabtagene ciloleucel, while none were reported with tisagenlecleucel. Despite low mortality, relapses increased clinical complexity and ICU requirements. Continuous monitoring and early management are essential to optimise outcomes. <h3>Conflict of Interest</h3> No conflict of interest

Indoleamine 2,3-dioxygenase 1 (IDO1) promotes immune effector cell-associated neurotoxicity syndrome (ICANS) after CAR-T therapy by disrupting brain endothelial cell integrity via KYNU–AA–Wnt/β-catenin pathway

Chimeric antigen receptor T-cell (CAR T-cell) therapy has revolutionized the treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We describe the real-world baseline characteristics, efficacy, safety, and post-relapse outcomes of adult patients with R/R LBCL who received CAR T-cell therapy at the University of California San Diego. A total of 66 patients with LBCL were treated with tisagenlecleucel or axicabtagene ciloleucel. The median age was 59.5, and 21% were over 70 years old. Additionally, 20% of the patients had an Eastern Cooperative Oncology Group (ECOG) performance score of ≥2. Cytokine release syndrome incidence was 88%; immune effector cell-associated neurotoxicity syndrome incidence was 56%. All-grade infection occurred in 48% of patients and in 79% of patients > 70 years old. Complete response (CR) was achieved in 53% and partial response in 14%. Median progression-free survival (PFS) was 10.3 months; median overall survival (OS) was 28.4 months. Patients who relapsed post-CAR T-cell therapy had poor outcomes, with a median OS2 of 4.8 months. Upon multivariate analysis, both ECOG (HR 2.65, 95% CI: 1.30-5.41; p = 0.007) and ≥2 sites of extranodal involvement (HR 2.22, 95% CI: 1.15-4.31; p = 0.018) were significant predictors of PFS. Twenty-six patients were R/R to CAR T-cell therapy; six patients were in remission at the time of data cut off, one of whom received allogeneic transplant. Overall, older patients can safely undergo CAR T-cell therapy, despite the increased risk of all-grade infection. In our cohort, ECOG performance score and ≥2 sites of extranodal disease are significant predictors of PFS.

Efficacy and Safety of Intravenous Chimeric Antigen Receptor T-Cell Therapy in Adults with Primary Central Nervous System Lymphoma: A Systematic Review and Meta-Analysis

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.

Cytomegalovirus (CMV) reactivation negatively impacts survival after CAR T-cell therapy in lymphoma patients: Results from the CART-SIE study

Plasma Cytokine and Chemokine Profiles Predict Efficacy and Toxicity of Anti-CD19 CAR-T Cell Therapy in Large B-Cell Lymphoma.

CARTITUDE-2: Efficacy and Safety of Ciltacabtagene Autoleucel, a B-Cell Maturation Antigen (BCMA)-Directed Chimeric Antigen Receptor T-Cell Therapy, in Patients with Multiple Myeloma and Early Relapse after Initial Therapy

Increased Cortical Glycolysis Following CD19 CART Therapy: A Radiographic Surrogate for an Altered Blood-Brain Barrier

Comparative efficacy and safety of bendamustine versus fludarabine and cyclophosphamide as lymphodepleting regimens for CAR-T therapy in hematological malignancies: A systematic review and meta-analysis