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Monoclonal antibody-based therapy as a new treatment strategy in multiple myeloma

Leukemia volume 26, pages 199–213 (2012)Cite this article

Abstract

The introduction of autologous stem cell transplantation combined with the introduction of immunomodulatory drugs (IMiDs) and proteasome inhibitors has significantly improved survival of multiple myeloma patients. However, ultimately the majority of patients will develop refractory disease, indicating the need for new treatment modalities. In preclinical and clinical studies, promising results have been obtained with several monoclonal antibodies (mAbs) targeting the myeloma tumor cell or the bone marrow microenvironment. The mechanisms underlying the therapeutic efficacy of these mAbs include direct induction of tumor cell apoptosis via inhibition or activation of target molecules, complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC). The capability of IMiDs to enhance ADCC and the modulation of various important signaling cascades in myeloma cells by both bortezomib and IMiDs forms the rationale to combine these novel agents with mAbs as new treatment strategies for myeloma patients. In this review, we will give an overview of various mAbs directly targeting myeloma tumor cells or indirectly via effects on the bone marrow microenvironment. Special focus will be on the combination of these mAbs with IMiDs or bortezomib.

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Acknowledgements

We thank Dr Constantine S Mitsiades (Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA) for useful discussions and comments on the manuscript.

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  1. Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands

    N W C J van de Donk, S Kamps & H M Lokhorst

  2. Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands

    T Mutis

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  1. N W C J van de Donk
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Correspondence to N W C J van de Donk.

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ND: research funding/contracted research—Celgene. HL: research funding/contracted research—Celgene, Genmab and Ortho-Biotech. SK and TM: none.

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van de Donk, N., Kamps, S., Mutis, T. et al. Monoclonal antibody-based therapy as a new treatment strategy in multiple myeloma. Leukemia 26, 199–213 (2012). https://doi.org/10.1038/leu.2011.214

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