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2084 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)

Program: Oral and Poster Abstracts
Session: 704. Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical Research, Real-world evidence, Adverse Events
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Maria Isabel Arbelaez Monroy, MD1*, Nil Albiol, MD2*, Alexandra Martínez-Roca2,3*, Nuria Martínez-Cibrián, MD4*, Cristina Arnaldos5*, Marta Español-Rego6*, Sergio Navarro-Velazquez7*, Helena Brillembourg1*, Beatriz Merchan1*, Leticia Alserawan8*, Maria Castella7*, Daniel Benitez-Ribas9*, Mercedes Montoro-Lorite10*, Pilar Ayora2*, Carla Ramos4*, Carlos Fernández de Larrea, MD11, E. Azucena González-Navarro1*, Alvaro Urbano-Ispizua, MD, PhD1, Jordi Esteve Reyner1, Manel Juan12*, Julio Delgado, MD, PhD1*, Luis Gerardo Rodríguez-Lobato13* and Valentin Ortiz-Maldonado, MD, PhD, MSc14

1Hematology Department, Hospital Clínic de Barcelona, Barcelona, Spain., Barcelona, Spain
2Hematology Department, Hematology Department, Hospital Clínic Barcelona, Barcelona, Spain, Barcelona, Spain
3Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Spain
4Hematology Department, Hospital Clínic Barcelona, Barcelona, Spain, Barcelona, Spain
5Immunology Department, Hospital Clínic de Barcelona, Barcelona, Spain., Barcelona, Barcelona, Spain
6Immunology Department, Hospital Clínic de Barcelona, Barcelona, Spain., Barcelona, Spain
7Immunology Department, Hospital Clínic de Barcelona, Barcelona, Spain., Barcleona, Spain
8Hospital Clínic de Barcelona, Barcelona, Spain
9Department of Immunology, Hospital Clínic de Barcelona, Barcelona, Spain., Barcelona, ESP
10Hematology Department, Hospital Clínic de Barcelona, Barcelona, Spain., Barcelona, ESP
11Hosp. Clinic I Provincial de Barcelona, Barcelona, Spain
12Immunology Department, Hospital Clínic de Barcelona, Barcelona, Spain, Plataform of Immunotherapy Clínic-Sant Joan de Déu, Barcelona; Spain, Barcelona, ESP
13Department of Hematology, Hospital Clínic de Barcelona, Barcelona, Spain., Barcelona, Spain
14Hematology Department, Hematology Department, Hospital Clínic Barcelona, Barcelona, Spain, Barcelona, ESP

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-HT received one and two doses, respectively. The high-HT group presented a higher incidence of fever (64% vs 21%; p=0.01) and CRS (55% vs 22%; p=0.02) as well as infections (61% vs 21% p=0.02), bacterial mainly (55%) in contrast with the low-HT group. Early ICAHT occurred in 82.6% and late in 91.3% of patients, though not statistically significant, high-HT patients presented grades 3 or 4 of ICAHT compared to those with low-HT (28% vs 7%). Hence, the aplastic phenotype was more frequent in high-HT patients (39.4% vs 14.3%, p=ns). The requirement for blood products was more frequent in the high-HT group as expected (45% vs 7%; p=0.02). No differences were observed in DOR, PFS, or OS (p=0.6). Finally, we did not find differences between high and low HT either in the expansion peak (median 6.66 cells/µl vs 3.53 cells/µl, p=0.3) or AUC at 30d (median 81.82 μl/l vs 61.59 μl/l, p=0.2).

Conclusion:

The CAR-HEMATOTOX score at lymphodepletion predicts inflammatory complications and transfusion dependence by identification of a high-risk group in our R/R BCP-ALL cohort, that can help us design individual prophylaxis and support strategies, as well as select patients for outpatient infusion and follow-up.

Disclosures: Albiol: KernPharma: Other: Travel grant; Beigene: Other: Travel grants; Adaptive Biotechnologies: Research Funding; Janssen: Honoraria, Other: Travel Expenses; AstraZeneca: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Other: Travel grants, Research Funding; Kite: Honoraria, Other: travel grant; Lilly: Other: travel grant. Martínez-Roca: Kite/Gilead: Honoraria, Other: Travel Grant; Abbvie: Honoraria, Other: Travel Grant; Pfizer: Honoraria. Martínez-Cibrián: Kite/Gilead: Honoraria, Other: Travel Expenses. Fernández de Larrea: Cellectar Biosciences: Research Funding; BeiGene: Consultancy, Honoraria, Other: Travel Expenses; Janssen: Consultancy, Honoraria, Other: Travel Expenses, Research Funding; Sanofi: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Takeda: Honoraria, Research Funding; Pfizer: Honoraria; BMS: Consultancy, Honoraria, Research Funding. Rodríguez-Lobato: Menarini Stemline: Honoraria; Sanofi: Honoraria; GSK: Honoraria; Amgen: Honoraria; Janssen: Honoraria. Ortiz-Maldonado: Pfizer: Honoraria; Miltenyi: Honoraria; Kite/Gilead: Honoraria, Other: Travel grants; Janssen: Honoraria, Other: Travel grants; Celgene-BMS: Honoraria, Other: Travel grants; Hospital Clínic de Barcelona: Current Employment; Novartis: Honoraria.

*signifies non-member of ASH