CAR-T Cell Therapy in Primary Mediastinal B-cell Lymphoma
DOI:
https://doi.org/10.61173/b3sbkj31Keywords:
CAR-T Cell Therapy, CAR19, Primary Mediastinal B-cell LymphomaAbstract
A specific type of CAR-T cell therapy, the CAR19 therapy has demonstrated notable efficacy for relapsed or refractory (R/R) hematologic cancers, including B-cell lymphomas. After the recent reclassification of the rare subtype Primary Mediastinal B-cell Lymphoma (PMBCL) from general Diffuse Large B-cell Lymphoma (DLBCL), questions have been raised about the application of immunotherapies in this cancer, including the most discussed CAR-T cell therapy. The CAR-T cell therapy, more specifically the CAR19, exerts anti-tumor effects in multiple mechanisms, including different cytotoxic pathways—apoptosis triggering via perforin–granzyme release and Fas/FasL-pathway—driven by calcium-dependent signaling MAPK, PI3K/Akt, and NF-κB. Multiple extant clinical trials have evaluated the response of PMBCL patients to CAR19, specifically the Axi-cel, Liso-cel, and Tisa-cel therapies, focusing the rates of complete response (CR), progression-free survival (PFS), and the overall survival (OS). Studies exclusive to PMBCL patients showed that bridging therapies and other first-line treatments did not influence CAR19 effectiveness, while post-relapse application of Pembrolizumab yielded durable CRs in some patients, and allo-HSCT was associated with high mortality. The CAR-SIE trial in Italy, comparing Axi-cel CAR19 in PMBCL cancer with other B-cell lymphomas, demonstrated a better result in PMBCL patients with higher ORR, CR, and PFS. This paper integrates the underlying mechanisms of CAR19 with clinical trials, aiming to demonstrate both the potential and the limitations of this therapy in PMBCL cancer.
References
[1] Volzone, F., Becchimanzi, C., Crisci, S., De Chiara, A., Porto, A., Caronna, A., Cuccaro, A., Sarno, S., Mallardo, D., Cagini, L., De Filippi, R., & Pinto, A. (2024). Long-term complete remission in a patient with high-risk primary mediastinal B-cell lymphoma and iatrogenic symptomatic bradycardia after only two courses of DA-EPOCH-R followed by chemo-free treatment. Annals of Hematology, 103(11), 4759–4764. https:// doi.org/10.1007/s00277-024-05994-4
[2] Chiappella, A., Casadei, B., Chiusolo, P., Di Rocco, A., Ljevar, S., Magni, M., Angelillo, P., Barbui, A. M., Cutini, I., Dodero, A., Bonifazi, F., Tisi, M. C., Bramanti, S., Musso, M., Farina, M., Martino, M., Novo, M., Grillo, G., Patriarca, F., & Zacchi, G. (2024). Axicabtagene ciloleucel treatment is more effective in primary mediastinal large B-cell lymphomas than in diffuse large B-cell lymphomas: the Italian CART-SIE study. Leukemia. https://doi.org/10.1038/s41375-024-02213-x
[3] Benmebarek, M.-R., Karches, C. H., Cadilha, B. L., Lesch, S., Endres, S., & Kobold, S. (2019). Killing Mechanisms of Chimeric Antigen Receptor (CAR) T Cells. International Journal of Molecular Sciences, 20(6), 1283. https://doi.org/10.3390/ ijms20061283
[4] Wu, L., Wei, Q., Brzostek, J., & Gascoigne, N. R. J. (2020). Signaling from T cell receptors (TCRs) and chimeric antigen receptors (CARs) on T cells. Cellular & Molecular Immunology, 17(6), 600–612. https://doi.org/10.1038/s41423-020-0470-3
[5] Liu, F., Bardhan, K., Yang, D., Thangaraju, M., Ganapathy, V., Waller, J. L., Liles, G. B., Lee, J. R., & Liu, K. (2012). NF-κB Directly Regulates Fas Transcription to Modulate Fas-mediated Apoptosis and Tumor Suppression. Journal of Biological Chemistry, 287(30), 25530–25540. https://doi.org/10.1074/jbc. M112.356279
[6] Wei, S., Gamero, A. M., Liu, J. H., Daulton, A. A., Valkov, N. I., Trapani, J. A., Larner, A. C., Weber, M. J., & Djeu, J. Y. (1998). Control of Lytic Function by Mitogen-activated Protein Kinase/ Extracellular Regulatory Kinase 2 (ERK2) in a Human Natural Killer Cell Line: Identification of Perforin and Granzyme B Mobilization by Functional ERK2. Journal of Experimental Medicine, 187(11), 1753–1765. https://doi.org/10.1084/ jem.187.11.1753
[7] Galtier, J., Mesguich, C., Sesques, P., Dupont, V., Bachy, E., Di Blasi, R., Thieblemont, C., Gastinne, T., Cartron, G., Brisou, G., Gros, F., Decroocq, J., Morschhauser, F., Rubio, M., Drieu La Rochelle, L., Le Bras, F., Carras, S., Chauchet, A., Bay, J., & Joris, M. (2025). Outcomes of patients with relapsed or refractory primary mediastinal B‐cell lymphoma treated with anti‐CD19 CAR‐T cells: CARTHYM, a study from the French national DESCAR‐T registry. HemaSphere, 9(2). https://doi. org/10.1002/hem3.70091
[8] Geva, M., Fried, S., Itzhaki, O., Shem-Tov, N., Danylesko, I., Yerushalmi, R., Marcus, R., Sdayoor, I., Shapira-Frommer, R., Kedmi, M., Shouval, R., Nagler, A., Shimoni, A., & Avigdor, A. (2023). P1400: THREE YEARS OUTCOMES OF PRIMARY MEDIASTINAL B CELL LYMPHOMA PATIENTS FOLLOWING ANTI CD19 CAR-T CELL THERAPY - A SINGLE CENTER EXPERIENCE. HemaSphere, 7(S3), e62933fb. https://doi.org/10.1097/01.hs9.0000972488.62933.fb
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