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)

The Easix (Endothelial Activation and Stress Index) Score Predicts for CAR T Related Toxicity in Patients Receiving Axicabtagene Ciloleucel (axi-cel) for Non-Hodgkin Lymphoma (NHL)

Predictors and Outcomes of Immune Effector Cell Associated Neurotoxicity Syndrome in Patients Receiving Chimeric Antigen Receptor T-Cell Therapy for Aggressive B-Cell Non-Hodgkin Lymphoma

EASIX Does Not Add Prognostic Value Beyond Lactate Dehydrogenase and ECOG Performance Status in CAR T-Cell Therapy: A GETH-TC Study.

CAR T-cell therapy for solid tumours

BackgroundChimeric antigen receptor (CAR) T-cell therapy has demonstrated significant benefits in the treatment of relapsed/refractory multiple myeloma (RRMM). However, these outcomes can be compromised by severe complications, including cytokine release...

Chimeric Antigen Receptor T Cells: Toxicity and Management Considerations

Easix Predicts Severe Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neuro-Toxicity Syndrome (ICANS) in Patients Receiving CD19-Directed Chimeric Antigen Receptor T (CAR-T) Cell Therapy

EASIX and m-EASIX predict CRS and ICANS in pediatric and AYA patients after CD19-CAR T-cell therapy

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

Factors Associated with Prolonged CRS and Neurotoxicity after Treatment with Axicabtagene Ciloleucel

Modified EASIX predicts severe cytokine release syndrome and neurotoxicity after chimeric antigen receptor T cells

BMS-986393 (CC-95266), a G Protein-Coupled Receptor Class C Group 5 Member D (GPRC5D)-Targeted Chimeric Antigen Receptor (CAR) T-Cell Therapy for Relapsed/Refractory Multiple Myeloma (RRMM): Updated Results from a Phase 1 Study

Risk factors for cytokine release syndrome and neurotoxicity in patients receiving epcoritamab or glofitamab for large B cell lymphoma: A multi-center, retrospective, real world analysis.

Simple SummaryCAR T-cell therapy became standard of care for patients with relapsed or refractory large B-cell lymphoma. However, their administration can be accompanied by toxicities, such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. It is important to identify patients at risk for these toxicities in order to start an early intervention in high-risk patients and guide outpatient CAR T-cell treatment. As a consequence, several easy-to-use risk scores including the EASIX and its derivatives were developed. However, in the available studies, disparities existed among the used endpoints and cutoff values, hampering the utility of these tools in practice. This study aims to validate these EASIX scores in a population-based cohort. This can be used to select the best predictive model and to further guide optimization of the proposed risk scores.Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) can hamper the clinical benefit of CAR T-cell therapy in patients with relapsed/refractory large B-cell lymphoma (r/r LBCL). To assess the risk of CRS and ICANS, the endothelial activation and stress index (EASIX), the modified EASIX (m-EASIX), simplified EASIX (s-EASIX), and EASIX with CRP/ferritin (EASIX-F(C)) were proposed. This study validates these scores in a consecutive population-based cohort. Patients with r/r LBCL treated with axicabtagene ciloleucel were included (n = 154). EASIX scores were calculated at baseline, before lymphodepletion (pre-LD) and at CAR T-cell infusion. The EASIX and the s-EASIX at pre-LD were significantly associated with ICANS grade ≥ 2 (both p = 0.04), and the EASIX approached statistical significance at infusion (p = 0.05). However, the predictive performance was moderate, with area under the curves of 0.61–0.62. Validation of the EASIX-FC revealed that patients in the intermediate risk group had an increased risk of ICANS grade ≥ 2 compared to low-risk patients. No significant associations between EASIX scores and CRS/ICANS grade ≥ 3 were found. The (m-/s-) EASIX can be used to assess the risk of ICANS grade ≥ 2 in patients treated with CAR T-cell therapy. However, due to the moderate performance of the scores, further optimization needs to be performed before broad implementation as a clinical tool, directing early intervention and guiding outpatient CAR T-cell treatment.

Utilization of Investigations for Neurotoxicity in CD19 and BCMA CART Recipients