Dados do Resumo

Título

Clinical impact of CD19 CAR T cell therapy in B cell malignancies: a systematic review and meta-analysis

Introdução

Chimeric antigen receptors (CARs) are artificial cell membrane receptors responsible for immune cell activation. They are constituted by an extracellular binding domain selected against an antigen, usually in the form of a single-chain variable fragment (scFv), a hinge sequence, and a transmembrane domain fused to intracellular costimulatory and stimulatory signaling domains. One of the current most effective CAR T cell therapies targets CD19, an antigen expressed by B cells in all stages of development until differentiation in plasmocytes, including B cell malignancies, such as Hodgkin (HL) and non-Hodgkin lymphoma (NHL), acute (ALL) or chronic lymphocytic leukemia (CLL). However, long-term disease-free survival is still a challenge to overcome.

Objetivo

Here, we evaluated the influence of different hinge, transmembrane (TM), and costimulatory CAR domains, as well as manufacturing conditions, cellular product type, doses, patient’s age, and tumor types on the clinical outcomes of patients with B cell cancers treated with CD19 CAR T cells.

Métodos

We accomplished a systematic review and meta-analysis according to the PRISMA statement registered on PROSPERO (CRD42022360268). Fifty-six studies (3493 patients) were included in the systematic review and 46 (3421patients) in the meta-analysis. The covariates considered were the type of hinge, TM, and costimulatory domains in the CAR, CAR T cell manufacturing conditions, cell population transduced with the CAR, the number of CAR T cell infusions, amount of CAR T cells injected/Kg, CD19 CAR type (name), tumor type, and age.

Resultados

The overall BCR rate was 56%, with 60% OS and 75% BOR. Younger patients displayed remarkably higher BCR prevalence without differences in OS. The presence of CD28 in the CAR’s hinge, TM, and costimulatory domains improved all outcomes evaluated. Doses from one to 4.9 million cells/kg resulted in better clinical outcomes. Our data also suggest that regardless of whether patients have had high objective responses, they might have survival benefits from CD19 CAR T therapy.

Conclusões

This meta-analysis is a critical hypothesis-generating instrument, capturing effects in the CD19 CAR T cells literature lacking randomized clinical trials and large observational studies.

Financiador do resumo

FAPESP 2018/17656-0; 2023/03631-3 and 2023/00925-6; CNPq 143179/2021-7 and 140514/2022-8

Palavras Chave

CAR-T Cell; Câncer; Clinical Oncology