Risk factors for, and reversibility of, peripheral neuropathy associated with bortezomib-melphalan-prednisone in newly diagnosed patients with multiple myeloma: Subanalysis of the phase 3 VISTA study

Meletios A. Dimopoulos, Maria Victoria Mateos, Paul G. Richardson, Rudolf Schlag, Nuriet K. Khuageva, Ofer Shpilberg, Martin Kropff, Ivan Spicka, Antonio Palumbo, Ka Lung Wu, Dixie Lee Esseltine, Kevin Liu, William Deraedt, Andrew Cakana, Helgi Van De Velde, Jesús F. San Miguel

Research output: Contribution to journalArticlepeer-review

111 Scopus citations

Abstract

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).

Original languageEnglish
Pages (from-to)23-31
Number of pages9
JournalEuropean Journal of Haematology
Volume86
Issue number1
DOIs
StatePublished - 1 Jan 2011
Externally publishedYes

Keywords

  • Bortezomib
  • Multiple myeloma
  • Peripheral neuropathy
  • Phase 3
  • Subanalysis
  • VISTA

ASJC Scopus subject areas

  • Hematology

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