Single-Agent Bortezomib in Previously Untreated Multiple Myeloma: Efficacy, Characterization of Peripheral Neuropathy, and Molecular Correlations With Response and Neuropathy
| Autor: | Hannah R. Briemberg, Asher Chanan-Khan, Robert L. Schlossman, L. Thompson Heffner, Nikhil C. Munshi, David Avigan, Wanling Xie, Dixie Lee Esseltine, Deborah Doss, Hani Hassoun, Anthony A. Amato, David J. Kuter, Patrick Y. Wen, Kenneth C. Anderson, Paul G. Richardson, Edie Weller, Sagar Lonial, Santosh Kesari, Anne Louise Oaklander, Constantine S. Mitsiades |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Antineoplastic Agents Gastroenterology Bortezomib Polyneuropathies Internal medicine Immunopathology medicine Humans Protease Inhibitors Multiple myeloma Aged business.industry Peripheral Nervous System Diseases Drug Synergism Middle Aged medicine.disease Boronic Acids Surgery Transplantation Treatment Outcome Peripheral neuropathy medicine.anatomical_structure Oncology Drug Resistance Neoplasm Pyrazines Proteasome inhibitor Female Bone marrow Neoplasm Recurrence Local Multiple Myeloma business Polyneuropathy Stem Cell Transplantation medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 27:3518-3525 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 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 treatment-emergent neuropathy, which will require future study. Conclusion Single-agent bortezomib is effective in previously untreated myeloma. Baseline myeloma-associated neuropathy seems more common than previously reported, and bortezomib-associated neuropathy, although a common toxicity, is reversible in most patients. |
| Databáze: | OpenAIRE |
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