Background: CAR T-cell therapy represents a breakthrough in cancer treatment as a cell-based
emerging immunotherapy with unprecedented success in relapsed or refractory hematological
malignancies such as lymphoma, certain types of leukemia, and multiple myeloma. Patients’ own T-
lymphocytes are genetically engineered to express a chimeric antigen receptor to harness and
reactivate cancer antigen-specific recognition in an HLA-unrestricted manner and thus, destroy
malignant cells. Current targets are CD19 and BCMA antigens, with 6 approved CAR T-cell products.
No evidence exists on biomarkers predictive of clinical response, overall survival, and/or toxicity
following CAR T-cells infusion. Polymorphisms identified on the genes encoding for immune
inhibitory molecules, – also referred to as checkpoints –, have been described to predispose to
cancer development and relapse after allogeneic hematopoietic stem cell transplantation, the
current treatment of choice for several hematologic cancers. Despite CAR T-cell therapy’s massive
therapeutic potential, significant challenges remain to be overcome for better and broader
applications, including unwanted potential toxicity, systemic immunogenicity, slow and complex
manufacturing, and high cost.
Objectives: To determine if the genotypes of CTLA-4, PD-1, LAG-3, BTLA, and CD200 immune
inhibitory checkpoints are associated with the incidence of Cytokine Release Syndrome (CRS) and
Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS) and can be predictive of overall
survival, disease-free survival, and response after CAR T-cell therapy.
Design & Methods: A prospective-multicenter cohort study, framed in the Spanish Group Terapia
Avanzada CAR T (TACART), setting up a collection of samples shipped to Girona from authorized CAR
T Spanish hospitals. DNA is extracted and stored at the IdIBGi Biobank and genotyping is performed
using RT-PCR. Univariate and multivariate analyses are performed.
Participants: Patients with aggressive hematological malignancies after ≥ 2 lines of treatment that
are candidates to undergo CAR T-cell immunotherapy in Spanish hospitals
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