TY - JOUR
T1 - Single-agent bortezomib in previously untreated multiple myeloma
T2 - Efficacy, characterization of peripheral neuropathy, and molecular correlations with response and neuropathy
AU - Richardson, Paul G.
AU - Xie, Wanling
AU - Mitsiades, Constantine
AU - Chanan-Khan, Asher A.
AU - Lonial, Sagar
AU - Hassoun, Hani
AU - Avigan, David E.
AU - Oaklander, Anne Louise
AU - Kuter, David J.
AU - Wen, Patrick Y.
AU - Kesari, Santosh
AU - Briemberg, Hannah R.
AU - Schlossman, Robert L.
AU - Munshi, Nikhil C.
AU - Heffner, L. Thompson
AU - Doss, Deborah
AU - Esseltine, Dixie Lee
AU - Weller, Edie
AU - Anderson, Kenneth C.
AU - Amato, Anthony A.
PY - 2009/7/20
Y1 - 2009/7/20
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.2008.18.3087
DO - 10.1200/JCO.2008.18.3087
M3 - Article
C2 - 19528374
AN - SCOPUS:70249146895
SN - 0732-183X
VL - 27
SP - 3518
EP - 3525
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 21
ER -