Single-agent bortezomib in previously untreated multiple myeloma: Efficacy, characterization of peripheral neuropathy, and molecular correlations with response and neuropathy

Paul G. Richardson, Wanling Xie, Constantine Mitsiades, Asher A. Chanan-Khan, Sagar Lonial, Hani Hassoun, David E. Avigan, Anne Louise Oaklander, David J. Kuter, Patrick Y. Wen, Santosh Kesari, Hannah R. Briemberg, Robert L. Schlossman, Nikhil C. Munshi, L. Thompson Heffner, Deborah Doss, Dixie Lee Esseltine, Edie Weller, Kenneth C. Anderson, Anthony A. Amato

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206 Scopus citations

Abstract

Purpose: To assess efficacy and safety of single-agent bortezomib in previously untreated patients with multiple myeloma, investigate prevalence of baseline and treatment-emergent polyneuropathy, and identify molecular markers associated with response and neuropathy. Patients and Methods: Patients received bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11, for up to eight 21-day cycles. A subset of patients underwent neurophysiologic evaluation pre- and post-treatment. Bone marrow aspirates were performed at baseline for exploratory whole-genome analyses. Results: Among 64 patients, 41% had partial response or better, including 9% complete/near-complete responses; median duration of response was 8.4 months. Response rates did not differ in the presence or absence of adverse cytogenetics. After median follow-up of 29 months, median time to progression was 17.3 months. Median overall survival had not been reached; estimated 1-year survival was 92%. Thirty-two patients successfully underwent optional stem-cell transplantation. Bortezomib treatment was generally well tolerated. At baseline, 20% of patients had sensory polyneuropathy. Sensory polyneuropathy developed during treatment in 64% of patients (grade 3 in 3%), but proved manageable and resolved in 85% within a median of 98 days. Neurologic examination, neurophysiologic testing, and measurements of epidermal nerve fiber densities in 35 patients confirmed pretreatment sensory neuropathy in 20% and new or worsening neuropathy in 63%. Pharmacogenomic analyses identified molecular markers of response and treatmentemergent neuropathy, which will require future study. Conclusion: Single-agent bortezomib is effective in previously untreated myeloma. Baseline myelomaassociated neuropathy seems more common than previously reported, and bortezomib-associated neuropathy, although a common toxicity, is reversible in most patients.

Original languageEnglish (US)
Pages (from-to)3518-3525
Number of pages8
JournalJournal of Clinical Oncology
Volume27
Issue number21
DOIs
StatePublished - Jul 20 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Richardson, P. G., Xie, W., Mitsiades, C., Chanan-Khan, A. A., Lonial, S., Hassoun, H., Avigan, D. E., Oaklander, A. L., Kuter, D. J., Wen, P. Y., Kesari, S., Briemberg, H. R., Schlossman, R. L., Munshi, N. C., Heffner, L. T., Doss, D., Esseltine, D. L., Weller, E., Anderson, K. C., & Amato, A. A. (2009). Single-agent bortezomib in previously untreated multiple myeloma: Efficacy, characterization of peripheral neuropathy, and molecular correlations with response and neuropathy. Journal of Clinical Oncology, 27(21), 3518-3525. https://doi.org/10.1200/JCO.2008.18.3087