title: 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.
abstract: OBJECTIVE
  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/m(2), days 1, 4, 8, 11, 22, 25, 29, 32, cycles 1-4, and days 1, 8, 22, 29, cycles 5-9; melphalan 9 mg/m(2), days 1-4, cycles 1-9; and prednisone 60 mg/m(2), 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/m(2). 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.
authors.affiliation: School of Medicine, University of Athens, Athens, Greece. mdimop@med.uoa.gr
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
authors.forename: Maria-Victoria
authors.initials: MV
authors.lastname: Mateos
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.forename: Rudolf
authors.initials: R
authors.lastname: Schlag
authors.forename: Nuriet K
authors.initials: NK
authors.lastname: Khuageva
authors.forename: Ofer
authors.initials: O
authors.lastname: Shpilberg
authors.forename: Martin
authors.initials: M
authors.lastname: Kropff
authors.forename: Ivan
authors.initials: I
authors.lastname: Spicka
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
authors.forename: Ka Lung
authors.initials: KL
authors.lastname: Wu
authors.forename: Dixie-Lee
authors.initials: DL
authors.lastname: Esseltine
authors.forename: Kevin
authors.initials: K
authors.lastname: Liu
authors.forename: William
authors.initials: W
authors.lastname: Deraedt
authors.forename: Andrew
authors.initials: A
authors.lastname: Cakana
authors.forename: Helgi
authors.initials: H
authors.lastname: Van De Velde
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000633:toxicity; D001897:Boronic Acids / Q000008:administration & dosage / Q000633:toxicity*; D000069286:Bortezomib; D005260:Female; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications* / Q000188:drug therapy*; D015999:Multivariate Analysis; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000209:etiology; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011719:Pyrazines / Q000008:administration & dosage / Q000633:toxicity*; D012307:Risk Factors
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D008558:Melphalan; D011241:Prednisone