Peripheral neuropathy during bortezomib treatment of multiple myeloma: a review of recent studies

Abstract

Treatment-emergent peripheral neuropathy (PN) is an important dose-limiting toxicity during treatment of multiple myeloma (MM). Bortezomib-induced PN (BIPN) occurred in 37–44% of clinical trial patients with MM, with the cumulative treatment dose as its single most significant predictor. This review discusses the clinical profile of BIPN in the treatment of MM and guidelines for its management. Lower rates of BIPN observed during treatment of solid tumors compared with rates of hematologic cancers are also discussed. Several areas of research are reviewed that may improve the management of BIPN, including co-therapies with the novel heat shock protein inhibitor tanespimycin, which appears to reduce the incidence of BIPN, and recent studies with second-generation proteasome inhibitors such as carfilzomib and NPI-0052. Adherence to the National Cancer Institute dose-modification algorithm is the most effective method for mitigating BIPN. Reversal of BIPN after treatment cessation occurs in most cases, but recovery in some patients takes as long as 1.7 years, and some individuals fail to return to baseline neurologic function. BIPN can cause a significant reduction in quality of life, primarily due to severe treatment-emergent pain. Ongoing research may provide additional information about the mechanism of BIPN and strategies to reduce PN.

Keywords:

• Peripheral neuropathy
• bortezomib
• multiple myeloma

Acknowledgements

The authors acknowledge the contribution of Mark Dana and AOI Communications, L.P., in the writing and editing of this report.

Declaration of interest: This study was sponsored by Bristol-Myers Squibb (and previously Kosan Biosciences).

Dr. Cavaletti has no relevant conflicts of interest to disclose. Dr. Jakubowiak is a consultant for Bristol-Myers Squibb, Exelixis Inc., and Millennium Pharmaceuticals; he is also on the Speakers' Bureau for Celgene Corporation, Millennium Pharmaceuticals, and Centocor Ortho Biotech Inc., and is on the Advisory Board for Millennium Pharmaceuticals.