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

Safety and Efficacy of BCMA-Targeted CAR-T Therapy in Geriatric Patients with Multiple Myeloma

e19556 Background: CD19 chimeric antigen receptor T cell therapy possesses unique side effects including cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS). Age is a major risk factor for ICANS. However, whether ICANS in older patients is different compared to younger patients is unknown. Herein, we report clinical course, outcomes and risk factors for ICANS in older patients with large B cell lymphoma (LBCL) treated with axicabtagene ciloleucel (axi-cel). Methods: We comprehensively reviewed detailed clinical courses of ICANS in 78 adult patients with LBCL treated with axi-cel between June 2016 and October 2020. Incidence, manifestation, risk factors, treatment, and outcomes of ICANS were compared between patients age ≥60 (n=32) and <60 (n=46) years old. Results: Baseline characteristics were comparable between older and younger patients except higher proportion of high international prognostic index and underlying cerebral microvascular disease in older patients. ICANS was observed in 16 patients in the older and 24 patients in the younger age group, with a 30-day incidence of 52% and 50%, respectively. Median time to CRS and ICANS were similar between 2 age groups. The most common initial neurological findings included aphasia, dysgraphia and encephalopathy in both age groups. Table summarizes the characteristics, clinical course and interventions of ICANS in older and younger patients. In Cox regression model, the presence of CRS was the only factor associated with ICANS in both age groups. Age, history of central nervous system involvement and cerebral microvascular disease were not associated with ICANS. Importantly, all patients had complete resolution of ICANS. No elderly patients in our cohort experienced seizure as a manifestation of ICANS. Conclusions: In our study, older age was not a risk factor for ICANS. CRS was the only factor associated with ICANS in both younger and older patients. Incidence, clinical course and neurological outcomes of ICANS in older patients treated with axi-cel were comparable to younger patients. [Table: see text]

Real-time interleukin-6 (IL-6) kinetics predict cytokine release syndrome (CRS) in patients receiving chimeric antigen receptor (CAR) T-cell therapy for Relapsed/Refractory B-cell malignancies

Safety and Efficacy of Two Anakinra Dose Regimens for Refractory CRS or Icans after CAR T-Cell Therapy

Unbiased Metabolomic Screening Reveals Pre-Existing Plasma Signatures in Large B-Cell Lymphoma Patients Treated with Anti-CD19 Chimeric Antigen Receptor (CAR) T-Cells: Association with Cytokine Release Syndrome (CRS) and Neurotoxicity (ICANS)

Clonal Hematopoiesis Is Associated with Severe Cytokine Release Syndrome in Patients Treated with Chimeric Antigen Receptor T-Cell (CAR-T) Therapy

Icans mitigation in high-risk elderly patients treated with CD28 co-stimulatory anti-CD19 CAR-T cells using a standardization protocol – a pilot study

Incidence and risk factors for immune effector cell-associated neurotoxicity syndrome in older patients with relapsed or refractory large B-cell lymphoma: A multicenter study

Safety and Efficacy of BCMA CAR-T Cell Therapy in Older Patients With Multiple Myeloma

High-dose anakinra to treat refractory immune effector cell-associated neurotoxicity syndrome in CAR T-cell therapy recipients

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

Utilization of Investigations for Neurotoxicity in CD19 and BCMA CART Recipients

Outcomes of CAR-T Cell Therapy for Large B Cell Lymphoma in Patients of 70 Years and Older: Multicentric Experience on Behalf of Geth-TC/Geltamo

CAR T-cell therapy for solid tumours

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)