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Bortezomib in Relapsed and Relapsed/Refractory Multiple Myeloma

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Bortezomib in the Treatment of Multiple Myeloma

Part of the book series: Milestones in Drug Therapy ((MDT))

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Abstract

Proteasome inhibition was validated as a rational therapeutic approach when bortezomib (VELCADE®), the first-in-class proteasome inhibitor, was approved by the Food and Drug Administration in 2003. This initial approval, which was for multiple myeloma patients who had received at least two prior therapies, and whose disease had demonstrated progression on the last of these, also made bortezomib the first new agent to be available for myeloma in over a decade. Since that time, further studies of bortezomib both alone, and as part of rationally designed, molecularly based combination regimens, have shown the versatility of this agent, and made it a universally accepted standard of care. Importantly, this use of bortezomib has been associated with ever increasing overall response rates and response qualities, and, most importantly, long-term outcome measures, including overall survival. These findings have rightfully entrenched bortezomib as one of the most important parts of our chemotherapeutic armamentarium against multiple myeloma. In this chapter, we will review the role of bortezomib as a single-agent, and in combination with other chemotherapeutics, to combat myeloma in the relapsed and relapsed/refractory settings. Also, emerging data about retreatment with bortezomib will be presented to provide insights into the possible role of this agent in the modern era, in which patients may have already been previously treated as part of induction therapy with bortezomib. Finally, approaches that show promise to overcome primary or secondary resistance to bortezomib will be examined, to determine if this agent may be of benefit in a number of myeloma settings in each individual patient.

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Acknowledgements

J.J.S. would like to acknowledge support from the National Cancer Institute (P01 CA124787). R.Z.O., a Leukemia & Lymphoma Society Scholar in Clinical Research, and would also like to acknowledge support from the National Cancer Institute (R01 CA102278 and P01 CA124787).

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Authors and Affiliations

  1. Department of Lymphoma & Myeloma, Division of Cancer Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    Jatin J. Shah & Robert Z. Orlowski

  2. Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 429, Houston, TX, 77030-4009, USA

    Robert Z. Orlowski

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Correspondence to Robert Z. Orlowski .

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Editors and Affiliations

  1. Dana-Farber Cancer Institute, Dept. Medical Oncology, Harvard Medical School, Binney St. 44, Boston, 02115, Massachusetts, USA

    Irene M. Ghobrial

  2. Dana-Farber Cancer Institute, Dept. Medical Oncology, Harvard Medical School, Binney St. 44, Boston, 02115, Massachusetts, USA

    Paul G. Richardson

  3. Dana-Farber Cancer Institute, Dept. Medical Oncology, Harvard Medical School, Binney St. 44, Boston, 02115, Massachusetts, USA

    Kenneth C. Anderson

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Shah, J.J., Orlowski, R.Z. (2011). Bortezomib in Relapsed and Relapsed/Refractory Multiple Myeloma. In: Ghobrial, I., Richardson, P., Anderson, K. (eds) Bortezomib in the Treatment of Multiple Myeloma. Milestones in Drug Therapy. Springer, Basel. https://doi.org/10.1007/978-3-7643-8948-2_6

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