CAR-T in Relapsed/Refractory Multiple Myeloma

Summary

The treatment options for multiple myeloma have evolved significantly over the years, providing patients with a range of therapies tailored to their specific circumstances. The choice of treatment often hinges on various factors, including the aggressiveness of the disease, individual prognostic indicators like genetic markers, the overall physical condition of the patient, and any pre-existing health issues that may affect treatment decisions. Current therapeutic strategies include several classes of drugs, each working through different mechanisms. Proteasome inhibitors (PIs) disrupt the protein degradation process within myeloma cells, thereby promoting their death. Immunomodulatory drugs (IMiDs) modulate the immune system and inhibit tumor growth by enhancing the body's natural anti-cancer responses. Monoclonal antibodies specifically target cancer cells, marking them for destruction by the immune system. In cases where patients are eligible, autologous stem cell transplantation remains a viable option, offering the potential for long-term remission by replacing damaged bone marrow with healthy stem cells from the patient's own body. Despite these advancements, multiple myeloma continues to present significant challenges, as it often recurs even after initial successful treatment and remains an incurable disease. This highlights the urgent need for innovative therapeutic strategies that can effectively address resistance to existing treatments, ultimately aiming to improve patient outcomes and survival rates.

Timeline

Start

2026-06-01

Primary completion

2027-12-31

Completion

2027-12-31

Publications

• Background Sommer C, Boldajipour B, Kuo TC, Bentley T, Sutton J, Chen A, Geng T, Dong H, Galetto R, Valton J, Pertel T, Juillerat A, Gariboldi A, Pascua E, Brown C, Chin SM, Sai T, Ni Y, Duchateau P, Smith J, Rajpal A, Van Blarcom T, Chaparro-Riggers J, Sasu BJ. Preclinical Evaluation of Allogeneic CAR T Cells Targeting BCMA for the Treatment of Multiple Myeloma. Mol Ther. 2019 Jun 5;27(6):1126-1138. doi: 10.1016/j.ymthe.2019.04.001. Epub 2019 Apr 8.
• Background Durie BG, Miguel JF, Blade J, Rajkumar SV. Clarification of the definition of complete response in multiple myeloma. Leukemia. 2015 Dec;29(12):2416-7. doi: 10.1038/leu.2015.290. Epub 2015 Oct 21. No abstract available.
• Background Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K, Gertz M, Dimopoulos M, Westin J, Sonneveld P, Ludwig H, Gahrton G, Beksac M, Crowley J, Belch A, Boccadaro M, Cavo M, Turesson I, Joshua D, Vesole D, Kyle R, Alexanian R, Tricot G, Attal M, Merlini G, Powles R, Richardson P, Shimizu K, Tosi P, Morgan G, Rajkumar SV; International Myeloma Working Group. International uniform response criteria for multiple myeloma. Leukemia. 2006 Sep;20(9):1467-73. doi: 10.1038/sj.leu.2404284. Epub 2006 Jul 20.
• Background Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 - Myeloma Academy. (2017, November 27). https://academy.myeloma.org.uk/resources/common-terminology-criteria-for-adverse-events-ctcae-version-5-0
• Background Buonato JM, Edwards JP, Zaritskaya L, Witter AR, Gupta A, LaFleur DW, Tice DA, Richman LK, Hilbert DM. Preclinical Efficacy of BCMA-Directed CAR T Cells Incorporating a Novel D Domain Antigen Recognition Domain. Mol Cancer Ther. 2022 Jul 5;21(7):1171-1183. doi: 10.1158/1535-7163.MCT-21-0552.
• Background Avery DT, Kalled SL, Ellyard JI, Ambrose C, Bixler SA, Thien M, Brink R, Mackay F, Hodgkin PD, Tangye SG. BAFF selectively enhances the survival of plasmablasts generated from human memory B cells. J Clin Invest. 2003 Jul;112(2):286-97. doi: 10.1172/JCI18025.

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