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


Authors: Richardson, P. G.; Xie, W. L.; 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.
Article Title: Single-agent bortezomib in previously untreated multiple myeloma: Efficacy, characterization of peripheral neuropathy, and molecular correlations with response and neuropathy
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/m(2) 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 treatment-emergent 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.
Keywords: thalidomide; myeloma; induction therapy; follow-up; stem-cell transplantation; refractory; phase-ii; plus dexamethasone; multicenter; apex trial; oncology-group
Journal Title: Journal of Clinical Oncology
Volume: 27
Issue: 21
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2009-07-01
Start Page: 3518
End Page: 3525
Language: English
ACCESSION: ISI:000268049100018
DOI: 10.1200/jco.2008.18.3087
PROVIDER: wos
PMCID: PMC2717758
PUBMED: 19528374
Notes: --- - Article - "Source: Wos"
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MSK Authors
  1. Hani Hassoun
    149 Hassoun