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<p>The treatment landscape for multiple myeloma is rapidly evolving, driven by T-cell-mediated tumor responses through CAR T-cell therapies and bispecific antibodies. Since KarMMa and CARTITUDE-1 established the activity of idecabtagene vicleucel and ciltacabtagene autoleucel in heavily pretreated disease, efforts have intensified to move them earlier, culminating in KarMMa-3 and CARTITUDE-4, which demonstrated superiority to standard regimens in earlier lines and prompted label expansions. Yet randomized data alone do not capture real-world effectiveness. Emerging cohorts highlight attrition before infusion, product-specific safety signatures with infection-driven non-relapse mortality, and heterogeneous outcomes in high-risk biology such as extramedullary disease, adverse cytogenetics, and early relapse. Access and delivery constraints, including bridging intensity, vein-to-vein intervals, out-of-specification release, and outpatient feasibility, further determine who benefits. This review synthesizes updated randomized and real-world evidence for idecabtagene vicleucel and ciltacabtagene autoleucel, examines challenging populations and emerging toxicities, and delineates operational factors that shape outcomes at scale. We outline where CAR T should displace existing standards, where caution is warranted, and which innovations in targets, constructs, and manufacturing are most likely to advance the start line.</p>

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CAR T-cells in multiple myeloma: the race to the start line

  • 期刊论文

  • 发表日期：

    2025年12月27日

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  • Abdul-Hamid Bazarbachi,
  • Divaya Bhutani,
  • Michael Sang Hughes,
  • Suzanne Lentzsch,
  • Markus Mapara,
  • Pawel Muranski,
  • Ran Reshef,
  • Tamna Wangjam,
  • Rajshekhar Chakraborty

摘要

The treatment landscape for multiple myeloma is rapidly evolving, driven by T-cell-mediated tumor responses through CAR T-cell therapies and bispecific antibodies. Since KarMMa and CARTITUDE-1 established the activity of idecabtagene vicleucel and ciltacabtagene autoleucel in heavily pretreated disease, efforts have intensified to move them earlier, culminating in KarMMa-3 and CARTITUDE-4, which demonstrated superiority to standard regimens in earlier lines and prompted label expansions. Yet randomized data alone do not capture real-world effectiveness. Emerging cohorts highlight attrition before infusion, product-specific safety signatures with infection-driven non-relapse mortality, and heterogeneous outcomes in high-risk biology such as extramedullary disease, adverse cytogenetics, and early relapse. Access and delivery constraints, including bridging intensity, vein-to-vein intervals, out-of-specification release, and outpatient feasibility, further determine who benefits. This review synthesizes updated randomized and real-world evidence for idecabtagene vicleucel and ciltacabtagene autoleucel, examines challenging populations and emerging toxicities, and delineates operational factors that shape outcomes at scale. We outline where CAR T should displace existing standards, where caution is warranted, and which innovations in targets, constructs, and manufacturing are most likely to advance the start line.