M-Easix (Better Than EASIX) Correlates with Specific Endotheliopathy Biomarkers, Predicts Severe CAR-T Cell Toxicities and Discriminates from Sepsis

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.3423-3423
• Main Authors: Moreno-Castaño, Ana Belén, Fernández, Sara, Brillembourg, Helena, de Moner, Blanca, Ventosa-Capell, Helena, Martinez-Sanchez, Julia, Ramos, Alex, Palomo, Marta, Molina, Patricia, Pino, Marc, Gomez-Ramirez, Pilar, Ortiz-Maldonado, Valentin, Martínez-Cibrián, Nuria, Delgado, Julio, Fernández de Larrea, Carlos, Salas Gay, Maria Queralt, Urbano-Ispizua, Alvaro, Téllez, Adrián, Nicolas, Jose Maria, Escolar, Ginés, Carreras, Enric, Fernández-Avilés, Francesc, Castro, Pedro, Diaz-Ricart, Maribel
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-208083

Background Chimeric antigen receptor (CAR)-T cell-based immunotherapy has become a groundbreaking advance for relapsed/refractory hematologic malignancies' treatment. However, cytokine release (CRS) and immune effector cell-associated neurotoxicity (ICANS) syndromes are highly incident and life-threatening toxicities, in which endothelial damage plays a fundamental role in their pathophysiology. Higher EASIX (Endothelial Activation Stress Index) and modified-EASIX ((m-EASIX), which substitutes creatinine for C reactive protein (CRP)) values calculated peri- CAR T-cell infusion have been correlated with increased risk for CRS and ICANS. The present study aims to assess the applicability of EASIX and m-EASIX to predict severe toxicities and to discriminate from sepsis, which clinically might have overlapping symptoms. Methods Adults with relapsed/refractory hematological malignancies (CD19 positive or multiple myeloma), admitted to our center to receive immunotherapy with CAR-T cells with any construct available, were included prospectively from 2018 to 2024. Blood samples were collected: (A) before the CAR-T cell infusion (day zero); (B), 24-48h after; (C) at the suspicion of CRS; (D) 24-48h after immunomodulatory treatment for CRS; (E) at the suspicion of ICANS and (F) 24-48h after corticosteroid treatment for ICANS. The results of EASIX and m-EASIX were compared with those in septic patients from an independent cohort. Correlations between EASIX, m-EASIX and levels of biomarkers of endothelial dysfunction (sVCAM-1, sTNFRI, TM, ST2, Ang-2), innate immunity activation (NETs, sC5b-9) and hemostasis/fibrinolysis (VWF:Ag, ADAMTS-13, alpha-2-antiplasmin, PAI-1:Ag), that were previously measured in 62 of the patients, were assessed. Results One-hundred and ten patients treated with academic or commercially available CD19 or BCMA-targeted CAR T-cell product for hematological malignancies (n=87 with B-cell malignancies, n=23 with multiple myeloma) were included. Patients who developed CRS (n=64) presented a significant increase of m-EASIX at its clinical onset vs.post-infusional values (median ± interquartile range (IQR) 12.7 ± 29.7 vs. 2.8 ±7 respectively, p