Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, TN.
Sarah Cannon Research Institute, Nashville, TN.
Clin Lymphoma Myeloma Leuk. 2023 May;23(5):310-321. doi: 10.1016/j.clml.2023.01.017. Epub 2023 Feb 3.
Despite continued advances that have led to improved survival of patients with multiple myeloma (MM) over the years, MM remains largely incurable with overall survival in patients who have progressed after proteasome inhibitor, immunomodulatory drug, and anti-CD38 monoclonal antibody therapy measured in months. Better understanding of the immunopathology of MM has led to the discovery of newer treatment targets like B-cell maturation antigen (BCMA). BCMA is a tumor necrosis factor receptor superfamily expressed on normal B-lymphocytes and malignant plasma cells with a vital role in proliferation, maturation, and differentiation of normal and malignant plasma cells. Antibody drug conjugates, chimeric antigen receptor (CAR) T-cells and bispecific T-cell engagers targeting the BCMA antigen are now available within and outside of clinical trials for treatment of triple class refractory MM. This review article focuses on the evolution, safety, efficacy, and limitations of BCMA-directed CAR T-cell therapies. It also discusses the challenges unveiled by the incorporation of these CAR T-cells in the treatment paradigm of MM and deliberates on the future of CAR T-cell therapy within MM.
尽管多年来的不断进步使得多发性骨髓瘤 (MM) 患者的生存率得到了提高，但 MM 仍然基本上无法治愈，接受蛋白酶体抑制剂、免疫调节剂药物和抗 CD38 单克隆抗体治疗后进展的患者的总体生存率以月为单位进行衡量。对 MM 的免疫病理学的更好理解导致发现了新的治疗靶点，如 B 细胞成熟抗原 (BCMA)。BCMA 是一种肿瘤坏死因子受体超家族，在正常 B 淋巴细胞和恶性浆细胞上表达，在正常和恶性浆细胞的增殖、成熟和分化中起着至关重要的作用。抗体药物偶联物、嵌合抗原受体 (CAR) T 细胞和针对 BCMA 抗原的双特异性 T 细胞衔接器，目前在临床试验内外都可用于治疗三药难治性 MM。本文重点介绍了针对 BCMA 的 CAR T 细胞疗法的发展、安全性、疗效和局限性。它还讨论了在 MM 的治疗模式中纳入这些 CAR T 细胞所揭示的挑战，并就 MM 中的 CAR T 细胞治疗的未来进行了思考。
