Division of Oncology and Hematology, University of Nebraska Medical Center, Omaha, NE.
Division of Hematology, The University of North Carolina at Chapel Hill, Chapel Hill, NC.
J Clin Oncol. 2023 Sep 20;41(27):4416-4429. doi: 10.1200/JCO.23.00512. Epub 2023 Jul 20.
Historically, the outcomes for individuals with triple-class refractory and penta-drug refractory multiple myeloma (MM) have been poor because of a dearth of effective treatment options. However, the advent of chimeric antigen receptor (CAR) T-cell and T-cell redirecting bispecific antibody (BsAb) therapies has led to unprecedented response rates and durations of response in heavily relapsed/refractory (R/R) populations. Currently, two B-cell maturation antigen (BCMA)-directed CAR T-cell therapies (idecabtagene vicleucel and ciltacabtagene autoleucel) as well as one BCMA/CD3 BsAb (teclistamab) have been approved for late-line (greater than four previous lines) R/R MM in the United States. The purpose of this review is to analyze the recent data for these approved therapies as well as provide an overview of other related CAR T-cell and BsAb therapies under development, including non-BCMA-targeting agents. We review efficacy and safety considerations, with particular focus on cytokine release syndrome, neurotoxicity, and infection risk. The relative merits and limitations of each class of therapy are discussed, as well as the areas of unmet need with respect to optimal sequencing and supportive care measures. We examine the factors that challenge equitable access to these novel therapies across minoritized racial, ethnic, and socioeconomic populations. Although it is evident that CAR T-cell and BsAb therapies will transform treatment paradigms in MM for years to come, significant work remains to identify the optimal utilization of these novel therapies and ensure equitable access.
从历史上看,由于缺乏有效的治疗选择,三药耐药和五药耐药多发性骨髓瘤(MM)患者的预后一直很差。然而,嵌合抗原受体(CAR)T 细胞和 T 细胞重定向双特异性抗体(BsAb)疗法的出现,使得在重度复发/难治(R/R)人群中产生了前所未有的反应率和反应持续时间。目前,两种针对 B 细胞成熟抗原(BCMA)的 CAR T 细胞疗法(idecabtagene vicleucel 和 cilta-cabtagene autoleucel)以及一种 BCMA/CD3 BsAb(teclistamab)已在美国获得批准,用于晚期(大于四线)R/R MM。本文旨在分析这些已获批疗法的最新数据,并概述其他正在开发的相关 CAR T 细胞和 BsAb 疗法,包括非 BCMA 靶向药物。我们对疗效和安全性进行了评估,重点关注细胞因子释放综合征、神经毒性和感染风险。讨论了每种治疗类别的优缺点和局限性,以及在最佳治疗顺序和支持性护理措施方面存在的未满足需求。我们还研究了这些新型疗法在少数族裔、种族和社会经济地位不同的人群中公平获得的挑战因素。尽管很明显,CAR T 细胞和 BsAb 疗法将在未来几年彻底改变 MM 的治疗模式,但仍有大量工作需要确定这些新型疗法的最佳应用,并确保公平获得。