Predictive short/long-term efficacy biomarkers and resistance mechanisms of CD19-directed CAR-T immunotherapy in relapsed/refractory B-cell lymphomas
- PMID: 37051246
- PMCID: PMC10083339
- DOI: 10.3389/fimmu.2023.1110028
Predictive short/long-term efficacy biomarkers and resistance mechanisms of CD19-directed CAR-T immunotherapy in relapsed/refractory B-cell lymphomas
Abstract
Genetically modified T-cell immunotherapies are revolutionizing the therapeutic options for hematological malignancies, especially those of B-cell origin. Impressive efficacies of CD19-directed chimeric antigen receptor (CAR)-T therapy have been reported in refractory/relapsed (R/R) B-cell non-Hodgkin lymphoma (NHL) patients who were resistant to current standard therapies, with a complete remission (CR) rate of approximately 50%. At the same time, problems of resistance and relapse following CAR-T therapy have drawn growing attention. Recently, great efforts have been made to determine various factors that are connected to the responses and outcomes following CAR-T therapy, which may not only allow us to recognize those with a higher likelihood of responding and who could benefit most from the therapy but also identify those with a high risk of resistance and relapse and to whom further appropriate treatment should be administered following CAR-T therapy. Thus, we concentrate on the biomarkers that can predict responses and outcomes after CD19-directed CAR-T immunotherapy. Furthermore, the mechanisms that may lead to treatment failure are also discussed in this review.
Keywords: B-cell lymphoma; CAR-T therapy; biomarker; efficacy; refractory/relapse; resistance.
Copyright © 2023 Xu, Li, Wang and Cao.
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Figures
References
-
- Kochenderfer JN, Wilson WH, Janik JE, Dudley ME, Stetler-Stevenson M, Feldman SA, et al. . Eradication of b-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood (2010) 116(20):4099–102. doi: 10.1182/blood-2010-04-281931 - DOI - PMC - PubMed
-
- Schuster SJ, Tam CS, Borchmann P, Worel N, McGuirk JP, Holte H, et al. . Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive b-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol (2021) 22(10):1403–15. doi: 10.1016/S1470-2045(21)00375-2 - DOI - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
