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Severe irreversible bilateral hearing loss after bortezomib (VELCADE®) therapy in a multiple myeloma (MM) patient

Leukemia volume 19, pages 869–870 (2005)Cite this article

TO THE EDITOR

Molecular detection of novel molecular targets in multiple myeloma (MM) has given rise to exciting new therapeutic options for MM patients including the use of high-dose dexamethasone, thalidomide, revimid, bortezomib and early single or double autologous stem-cell transplantation.1 Bortezomib is a novel proteasome inhibitor which has recently been approved for the treatment of MM patients who received at least two prior therapies and progressed during the last treatment.2, 3, 4 It targets the 26S proteasome, which functions by eliminating cellular proteins tagged for degradation by polyubiquitin chains. Regulated ubiquitin-dependent proteolysis controls important events such as cell growth and proliferation, development, apoptosis, signal transduction, gene expression and immune response. Proteins entering the proteasome are stripped of their ubiquitin and degraded through catalytic processes within the core of the proteasome. Bortezomib induces apoptosis in various cancer cells, including MM and other lymphoma cells. It also affects nuclear factor-κB (NF-κB), the bone marrow (BM) microenvironment and various cytokine interactions, most importantly IL-6.2, 3, 4 Bortezomib has been shown to induce an impressive overall response rate of 35% in refractory and relapsed MM patients (pivotal phase-II (SUMMIT) trial).2 It was recently tested in an international phase-III (APEX) trial which randomly compared bortezomib and dexamethasone.5 Interim results have demonstrated that patients on bortezomib achieved a highly significant benefit in time to progression, overall survival (OS) and a trend towards a lower incidence of grade ⩾3 infections. Owing to the positive results with bortezomib, the Data Monitoring Committee recommended treatment on the dexamethasone arm to be stopped and patients randomized to dexamethasone were allowed to receive bortezomib. Adverse effects, such as asthenic conditions, nausea, diarrhea, anorexia, constipation, thrombocytopenia, peripheral neuropathy, pyrexia, vomiting and anemia were mostly mild.2, 3, 4

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Acknowledgements

We thank the internal reviewer in our institution for critically reading the manuscript and the anonymous external reviewer for thoughtful comments. The study was supported by Millennium Pharmaceuticals. The sponsor Millennium has received, carefully reviewed and fully agreed to this manuscript.

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Authors and Affiliations

  1. University Medical Center, Hematology and Oncology Department, Freiburg, Germany

    M Engelhardt, A M S Müller & R Wäsch

  2. Department of Otolaryngology, University of Freiburg, Germany

    W Maier

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  1. M Engelhardt
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  2. A M S Müller
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  3. W Maier
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  4. R Wäsch
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Correspondence to M Engelhardt.

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Engelhardt, M., Müller, A., Maier, W. et al. Severe irreversible bilateral hearing loss after bortezomib (VELCADE®) therapy in a multiple myeloma (MM) patient. Leukemia 19, 869–870 (2005). https://doi.org/10.1038/sj.leu.2403723

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