Medizinische Klinik und Poliklinik II und Lehrstuhl für zelluläre Immuntherapie, Medizinische Klinik II, Universitätsklinikum Würzburg, Würzburg, Germany.
Interdisziplinäres Zentrum für Klinische Forschung (IZKF), Universitätsklinikum Würzburg, Würzburg, Germany.
Leuk Lymphoma. 2024 Feb;65(2):143-157. doi: 10.1080/10428194.2023.2276676. Epub 2024 Jan 24.
Although the approval of new drugs has improved the clinical outcome of multiple myeloma (MM), it was widely regarded as incurable over the past decades. However, recent advancements in groundbreaking immunotherapies, such as chimeric antigen receptor T cells (CAR-T), have yielded remarkable results in heavily pretreated relapse/refractory patients, instilling hope for a potential cure. CAR-T are genetically modified cells armed with a novel receptor to specifically recognize and kill tumor cells. Among the potential targets for MM, the B-cell maturation antigen (BCMA) stands out since it is highly and almost exclusively expressed on plasma cells. Here, we review the currently approved BCMA-directed CAR-T products and ongoing clinical trials in MM. Furthermore, we explore innovative approaches to enhance BCMA-directed CAR-T and overcome potential reasons for treatment failure. Additionally, we explore the side effects associated with these novel therapies and shed light on accessibility of CAR-T therapy around the world.
虽然新药物的批准改善了多发性骨髓瘤（MM）的临床结局，但在过去几十年中，它被广泛认为是无法治愈的。然而，近年来，开创性的免疫疗法，如嵌合抗原受体 T 细胞（CAR-T），在经过大量预处理的复发/难治性患者中取得了显著的效果，为潜在的治愈带来了希望。CAR-T 是经过基因修饰的细胞，配备了一种新型受体，可以特异性识别和杀死肿瘤细胞。在 MM 的潜在靶点中，B 细胞成熟抗原（BCMA）引人注目，因为它在浆细胞上高度且几乎唯一表达。在这里，我们综述了目前批准用于 MM 的靶向 BCMA 的 CAR-T 产品和正在进行的临床试验。此外，我们还探讨了增强靶向 BCMA 的 CAR-T 和克服潜在治疗失败原因的创新方法。此外，我们还探讨了这些新型疗法相关的副作用，并阐明了全球范围内 CAR-T 治疗的可及性。
