The CAR-Hematotox Identifies Patients at High Risk of Infectious/Inflammatory Complications in a Cohort of Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) Treated with ARI-0001 (Varnimcabtagene Autoleucel)

• Published in: Blood 2024-11, Vol.144, p.2084-2084
• Main Authors: Arbelaez Monroy, Maria Isabel, Albiol, Nil, Martínez-Roca, Alexandra, Martínez-Cibrián, Nuria, Arnaldos, Cristina, Español-Rego, Marta, Navarro-Velazquez, Sergio, Brillembourg, Helena, Merchan, Beatriz, Alserawan, Leticia, Castella, Maria, Benitez-Ribas, Daniel, Montoro-Lorite, Mercedes, Ayora, Pilar, Ramos, Carla, Fernández de Larrea, Carlos, González-Navarro, E. Azucena, Urbano-Ispizua, Alvaro, Esteve Reyner, Jordi, Juan, Manel, Delgado, Julio, Rodríguez-Lobato, Luis Gerardo, Ortiz-Maldonado, Valentin
• Format: Article
• Language: English
• ISSN: 0006-4971
• DOI: 10.1182/blood-2024-206082

Introduction Chimeric antigen receptor T cells (CART) have improved outcomes in many hematologic malignancies. Cytopenia or ICAHT (immune effector cell-associated hematotoxicity) are common and pose a direct impact on procedure-related mortality. They raise a challenge in the short and long-term follow-up. The CAR-HEMATOTOX score (HT) uses ferritin, CRP, hemoglobin, platelet, and neutrophil count to predict the risk of hematological toxicities in CART receptors. It is validated in follicular, mantle-cell lymphoma, and large B-cell lymphoma. However, its usefulness remains unclear in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients treated with CAR T cells. Methods This is a single-center, retrospective, and observational study that includes R/R BCP-ALL adult patients treated with varnimcabtagene autoleucel (var-cel, ARI-0001), an autologous, second-generation, 4-1BB-based CD19-targeted CART product. This includes patients treated in the CART19-BE-01 trial and the consecutive compassionate use and hospital exemption program between July 2017 and November 2023. All patients were treated at Hospital Clínic (Barcelona, Spain). We retrospectively calculated CAR-HEMATOTOX at lymphodepletion for each patient and explored its association with several outcomes. Statistical analyses were performed with R v 4.3.2 and Graphpad Prism v 10.2. Results The first ten were excluded from 68 patients with BCP-ALL infused with var-cel, as they received the total dose in a single infusion (var-cel current label consists of a fractionated infusion in three consecutive days). A total of 58 BCP-ALL patients were analyzed. The median age at infusions was 38.5 years (range 20-73), 28 (43.3%) patients were female and 54 (93.1%) presented an ECOG between 0-1. Patients median lines of treatment were 3 (range 1-6), forty-seven (81%) of the patients had received at least 2 lines of treatment (median 3.7, 1-6) and 47 (81%) had also undergone allogeneic stem cell transplant. Twenty-three (48.9%) patients presented any infection during the admission period (8.6% two or more infections), 25 patients (44.6%) had CRS (only 1 grade ³3), and only 2 (3.6%) patients presented ICANS. The median follow-up of the whole cohort was 15 months (1.7-67.4). A high HT score was observed in 38 (68%) subjects. Patient characteristics (age, sex, ECOG) were equally distributed between groups, All patients in the low-HT group received the 3 fractionated doses, while 3 and 4 patients in the high-H