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Meta-Analysis
. 2024 Aug 22;24(1):1037.
doi: 10.1186/s12885-024-12651-6.

CD19 CAR T cells for B cell malignancies: a systematic review and meta-analysis focused on clinical impacts of CAR structural domains, manufacturing conditions, cellular product, doses, patient's age, and tumor types

Erik Montagna  1 , Najla Santos Pacheco de Campos  2   3 , Victoria Alves Porto  2 , Giselle Correia Próspero da Silva  2 , Eloah Rabello Suarez  4   5
Affiliations
Meta-Analysis

CD19 CAR T cells for B cell malignancies: a systematic review and meta-analysis focused on clinical impacts of CAR structural domains, manufacturing conditions, cellular product, doses, patient's age, and tumor types

Erik Montagna et al. BMC Cancer. .

Abstract

CD19-targeted chimeric antigen receptors (CAR) T cells are one of the most remarkable cellular therapies for managing B cell malignancies. However, long-term disease-free survival is still a challenge to overcome. 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. The primary outcome was defined as the best complete response (BCR), and the secondary outcomes were the best objective response (BOR) and 12-month overall survival (OS). 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. Fifty-six studies (3493 patients) were included in the systematic review and 46 (3421 patients) in the meta-analysis. 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. 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.

Keywords: 4-1BB; CAR T cell dose; CAR T cells manufacturing conditions; CD28; CD8; Clinical response CAR T cells; Costimulatory domain; Hinge; Transmembrane.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart for eligibility assessment according to PRISMA guidelines. Based on model reference(Page et al., 2021a). For more information, visit: http://www.prisma-statement.org/
Fig. 2
Fig. 2
The Forest Plot represents the overall rate of the primary outcome Best Complete Response (BCR) of patients treated with CD19 CAR T therapy based on the studies included in the meta-analysis
Fig. 3
Fig. 3
Funnel, Baujat, and Radial plots showing the heterogeneity observed for the primary outcome Best Complete Response (BCR) of patients treated with CD19 CAR T therapy based on the studies included in the meta-analysis
See this image and copyright information in PMC

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