Clinical and Biological Correlates of Resistance and Relapse After CD19-Directed CAR T-Cell Therapy in Large B-Cell Lymphoma: A Structured Narrative Review
4 affiliations
- 1Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba 80250-060, PR, Brazil
- 2Faculdades Pequeno Príncipe, Rebouças, Curitiba 80230-020, PR, Brazil
- 3Bioinformatics and Systems Biology Laboratory, Federal University of Paraná, Curitiba 81520-260, PR, Brazil
- 4Institut de Pharmacologie Moléculaire et Cellulaire CNRS UMR7275, Inserm U1423, Université Côte d’Azur, 06560 Valbonne, France
Abstract
Background/Objectives: CD19-directed chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of relapsed/refractory large B-cell lymphoma (r/r LBCL), yet primary resistance and relapse remain common. We evaluated how recent clinical and translational evidence refines established resistance frameworks and which knowledge gaps prevent the relative contribution of individual mechanisms from being determined. Methods: We conducted a structured narrative review of 14 selected clinical and translational studies addressing tumor-, product-, host-, and microenvironment-related dimensions of treatment failure, synthesized across four interpretive domains and compared with nine previous reviews. Results: Durable benefit was associated with favorable tumor and immune transcriptional programs and greater CAR T-cell fitness, expansion, or persistence. Treatment failure was associated with tumor-intrinsic resistance programs, exhausted T-cell states, systemic inflammatory signals, and suppressive tumor-microenvironment features, including PD-L1-expressing macrophages. Antigen escape remained relevant, but incomplete serial CD19 assessment precluded conclusions about its relative contribution. Comparison with earlier reviews showed continuity rather than replacement, with LBCL-focused evidence adding biological resolution. Conclusions: Resistance and relapse after CD19 CAR T-cell therapy in LBCL are multifactorial. Prospective longitudinal studies integrating tumor tissue, apheresis and manufactured products, peripheral blood, and matched relapse samples are needed to validate predictive biomarkers and guide rational treatment strategies.
Related
- Clinical utility and reproducibility of intravoxel incoherent motion MRI in rectal cancer: a structured narrative review
- Clinical evaluation of visual snow syndrome: a structured narrative review with proposed clinical diagnostic approach
- Giant Keratinocyte Carcinomas: Clinical, Histopathological, Molecular and Health-System Factors with Therapeutic Implications—A Structured Narrative Review
- Rhythmic dance interventions and dance/movement therapy for depression and anxiety: a structured narrative review of clinical evidence, candidate mechanisms, and implementation considerations
- Clinical correlates for fluconazole resistance in Candida bloodstream infections.
BibTeX
@article{resende2026clinical,
title = {{Clinical and Biological Correlates of Resistance and Relapse After CD19-Directed CAR T-Cell Therapy in Large B-Cell Lymphoma: A Structured Narrative Review}},
author = {Jean Silva de Souza Resende and Igor Samesima Giner and Maria Gabriela Custodio de Figueiredo and Mariana Martins Paraizo and Enzo Lalli and Bonald Cavalcante de Figueiredo},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18203370},
url = {https://www.mdpi.com/2072-6694/18/20/3370},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Clinical and Biological Correlates of Resistance and Relapse After CD19-Directed CAR T-Cell Therapy in Large B-Cell Lymphoma: A Structured Narrative Review
AU - Jean Silva de Souza Resende
AU - Igor Samesima Giner
AU - Maria Gabriela Custodio de Figueiredo
AU - Mariana Martins Paraizo
AU - Enzo Lalli
AU - Bonald Cavalcante de Figueiredo
PY - 2026
DA - 2026/10/01
JO - Cancers
DO - 10.3390/cancers18203370
UR - https://www.mdpi.com/2072-6694/18/20/3370
AB - Background/Objectives: CD19-directed chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of relapsed/refractory large B-cell lymphoma (r/r LBCL), yet primary resistance and relapse remain common. We evaluated how recent clinical and translational evidence refines established resistance frameworks and which knowledge gaps prevent the relative contribution of individual mechanisms from being determined. Methods: We conducted a structured narrative review of 14 selected clinical and translational studies addressing tumor-, product-, host-, and microenvironment-related dimensions of treatment failure, synthesized across four interpretive domains and compared with nine previous reviews. Results: Durable benefit was associated with favorable tumor and immune transcriptional programs and greater CAR T-cell fitness, expansion, or persistence. Treatment failure was associated with tumor-intrinsic resistance programs, exhausted T-cell states, systemic inflammatory signals, and suppressive tumor-microenvironment features, including PD-L1-expressing macrophages. Antigen escape remained relevant, but incomplete serial CD19 assessment precluded conclusions about its relative contribution. Comparison with earlier reviews showed continuity rather than replacement, with LBCL-focused evidence adding biological resolution. Conclusions: Resistance and relapse after CD19 CAR T-cell therapy in LBCL are multifactorial. Prospective longitudinal studies integrating tumor tissue, apheresis and manufactured products, peripheral blood, and matched relapse samples are needed to validate predictive biomarkers and guide rational treatment strategies.
SN - 2072-6694
ER -