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Chimeric antigen receptor T cell therapy in multiple myeloma: promise and challenges

Bone Marrow Transplantation volume 56, pages 9–19 (2021)Cite this article

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Abstract

Despite a sea change in the therapeutic landscape, multiple myeloma (MM), a cancer of antibody producing plasma cells, remains incurable requiring continued intervention for disease control. In this context, chimeric antigen receptor (CAR) T cell therapy has emerged as a promising immunotherapeutic approach with unprecedented results in heavily treated relapsed and/or refractory MM patients. Although B cell maturation antigen (BCMA) is the current lead target for CAR-T cell therapy in MM, several other antigenic targets are also being investigated. Relapses, however, are inevitable in spite of the promising early responses, and may be mediated by antigenic modulation, poor persistence and “immunostat” in tumor microenvironment. Akin to multi-agent chemotherapy, multi-targeted CAR-T antigens and combinatorial approaches are underway to overcome the resistance mechanisms. Further, CAR-T specific toxicity concerns such as cytokine release syndrome and neurotoxicity, as well as manufacturing time lag are other key challenges. Allogeneic CAR that offers “off-the-shelf” options, and mRNA transfected CAR are being developed to mitigate the access and safety issues. In this review we provide the comprehensive review of the most current clinical trial data for CAR-T in myeloma, challenges associated with this therapy and discuss its future in myeloma therapeutics.

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Fig. 1
Fig. 2: Challenges associated with CAR-T therapy in myeloma.
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Acknowledgements

We thank Theresa Camille Maatman (tmaatman@mcw.edu) for the graphics.

Funding

Takeda Pharmaceutical Company; Otsuka Pharmaceutical; Spectrum Pharmaceuticals; Consultancy Incyte Corporation; ADC Therapeutics; Celgene Corporation; Pharmacyclics, Magenta Therapeutics, Omeros, AbGenomics, Verastem, TeneoBio. Speaker’s Bureau: Sanofi Genzyme, AstraZeneca.

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  1. BMT and Cellular Therapy Program, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, 53226, USA

    Binod Dhakal, Parameswaran N. Hari & Mehdi Hamadani

  2. Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute/Atrium Health, Charlotte, NC, 28204, USA

    Saad Z. Usmani

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Dr. Dhakal has served on the advisory board of Takeda, Amgen and Jansen. He has received honorarium from Celgene. The remaining authors declare that they have no conflict of interest.

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Dhakal, B., Hari, P.N., Usmani, S.Z. et al. Chimeric antigen receptor T cell therapy in multiple myeloma: promise and challenges. Bone Marrow Transplant 56, 9–19 (2021). https://doi.org/10.1038/s41409-020-01023-w

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