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Multiple myeloma gammopathies

Development of CAR-T cell therapies for multiple myeloma

Leukemia volume 34, pages 2317–2332 (2020)Cite this article

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Abstract

Currently available data on chimeric antigen receptor (CAR)-T cell therapy has demonstrated efficacy and manageable toxicity in heavily pretreated multiple myeloma (MM) patients. The CAR-T field in MM is rapidly evolving with >50 currently ongoing clinical trials across all phases, different CAR-T design, or targets. Most of the CAR-T trials are performed in China and the United States, while European centers organize or participate in only a small fraction of current clinical investigations. Autologous CAR-T cell therapy against B cell maturation antigen shows the best evidence of efficacy so far but main issues remain to be addressed: duration of response, longer follow-up, prolonged cytopenia, patients who may benefit the most such as those with extramedullary disease, outcome prediction, and the integration of CAR-T cell therapy within the MM treatment paradigm. Other promising targets are, i.a.,: CD38, SLAMF7/CS1, or GPRC5D. Although no product has been approved to date, cost and production time for autologous products are expected to be the main obstacles for broad use, for which reason allogeneic CAR-T cells are currently explored. However, the inherent risk of graft-versus-host disease requires additional modification which still need to be validated. This review aims to present the current status of CAR-T cell therapy in MM with an overview on current targets, designs, and stages of CAR-T cell development. Main challenges to CAR-T cell therapy will be highlighted as well as strategies to structurally improve the CAR-T cell product, and thereby its efficacy and safety. The need for comparability of the most promising therapies will be emphasized to balance risks and benefits in an evidence-based but personalized approach to further improve outcome of patients with MM.

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Fig. 1: Number of currently ongoing CAR-T cell trials.

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Authors and Affiliations

  1. Department of Stem Cell Transplantation with Research Department Cell and Gene Therapy University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Nico Gagelmann, Kristoffer Riecken, Christine Wolschke, Carolina Berger, Francis A. Ayuk, Boris Fehse & Nicolaus Kröger

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  1. Nico Gagelmann
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  2. Kristoffer Riecken
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  7. Nicolaus Kröger
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Correspondence to Nicolaus Kröger.

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Gagelmann, N., Riecken, K., Wolschke, C. et al. Development of CAR-T cell therapies for multiple myeloma. Leukemia 34, 2317–2332 (2020). https://doi.org/10.1038/s41375-020-0930-x

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