TY - JOUR
T1 - Risk factors for, and reversibility of, peripheral neuropathy associated with bortezomib-melphalan-prednisone in newly diagnosed patients with multiple myeloma
T2 - Subanalysis of the phase 3 VISTA study
AU - Dimopoulos, Meletios A.
AU - Mateos, Maria Victoria
AU - Richardson, Paul G.
AU - Schlag, Rudolf
AU - Khuageva, Nuriet K.
AU - Shpilberg, Ofer
AU - Kropff, Martin
AU - Spicka, Ivan
AU - Palumbo, Antonio
AU - Wu, Ka Lung
AU - Esseltine, Dixie Lee
AU - Liu, Kevin
AU - Deraedt, William
AU - Cakana, Andrew
AU - Van De Velde, Helgi
AU - San Miguel, Jesús F.
PY - 2011/1
Y1 - 2011/1
N2 - Objectives: This subanalysis of the phase 3 VISTA trial aimed to assess the frequency, characteristics and reversibility of, and prognostic factors for, bortezomib-associated peripheral neuropathy (PN) in newly diagnosed patients with multiple myeloma ineligible for high-dose therapy who received bortezomib plus melphalan-prednisone.Methods: Patients received nine 6-wk cycles of VMP (bortezomib 1.3 mg/m2, days 1, 4, 8, 11, 22, 25, 29, 32, cycles 1-4, and days 1, 8, 22, 29, cycles 5-9; melphalan 9 mg/m2, days 1-4, cycles 1-9; and prednisone 60 mg/m2, days 1-4, cycles 1-9).Results: Overall, 47% of patients receiving VMP developed PN, including 19% grade 2 and 13% grade ≥3 (<1% grade 4). The PN incidence was dose-related and reached a plateau at a cumulative bortezomib dose of approximately 45 mg/m2. Median time to PN onset was 2.3 months. Bortezomib-associated PN was reversible; 79% of events improved by at least one NCI CTCAE grade within a median of 1.9 months and 60% completely resolved within a median of 5.7 months, with reversibility similar in responding and non-responding patients. By multivariate analysis, baseline neuropathy was the only consistent risk factor for any PN [hazard ratio (HR) 1.785, P = 0.0065], grade ≥2 PN (HR 2.205, P = 0.0032), and grade ≥3 PN (HR 2.438, P = 0.023); age, pre-existing diabetes, International Staging System stage, obesity, and creatinine clearance did not affect the overall rate of PN.Conclusions: Rates of bortezomib-induced PN in the frontline setting were similar to those in relapsed patients and resolved in most cases. (Clinicaltrials.gov identifier: NCT00111319).
AB - Objectives: This subanalysis of the phase 3 VISTA trial aimed to assess the frequency, characteristics and reversibility of, and prognostic factors for, bortezomib-associated peripheral neuropathy (PN) in newly diagnosed patients with multiple myeloma ineligible for high-dose therapy who received bortezomib plus melphalan-prednisone.Methods: Patients received nine 6-wk cycles of VMP (bortezomib 1.3 mg/m2, days 1, 4, 8, 11, 22, 25, 29, 32, cycles 1-4, and days 1, 8, 22, 29, cycles 5-9; melphalan 9 mg/m2, days 1-4, cycles 1-9; and prednisone 60 mg/m2, days 1-4, cycles 1-9).Results: Overall, 47% of patients receiving VMP developed PN, including 19% grade 2 and 13% grade ≥3 (<1% grade 4). The PN incidence was dose-related and reached a plateau at a cumulative bortezomib dose of approximately 45 mg/m2. Median time to PN onset was 2.3 months. Bortezomib-associated PN was reversible; 79% of events improved by at least one NCI CTCAE grade within a median of 1.9 months and 60% completely resolved within a median of 5.7 months, with reversibility similar in responding and non-responding patients. By multivariate analysis, baseline neuropathy was the only consistent risk factor for any PN [hazard ratio (HR) 1.785, P = 0.0065], grade ≥2 PN (HR 2.205, P = 0.0032), and grade ≥3 PN (HR 2.438, P = 0.023); age, pre-existing diabetes, International Staging System stage, obesity, and creatinine clearance did not affect the overall rate of PN.Conclusions: Rates of bortezomib-induced PN in the frontline setting were similar to those in relapsed patients and resolved in most cases. (Clinicaltrials.gov identifier: NCT00111319).
KW - Bortezomib
KW - Multiple myeloma
KW - Peripheral neuropathy
KW - Phase 3
KW - Subanalysis
KW - VISTA
UR - http://www.scopus.com/inward/record.url?scp=78650110658&partnerID=8YFLogxK
U2 - 10.1111/j.1600-0609.2010.01533.x
DO - 10.1111/j.1600-0609.2010.01533.x
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C2 - 20874823
AN - SCOPUS:78650110658
SN - 0902-4441
VL - 86
SP - 23
EP - 31
JO - European Journal of Haematology
JF - European Journal of Haematology
IS - 1
ER -