title: Bortezomib-induced peripheral neuropathy in multiple myeloma: a comparison between previously treated and untreated patients.
abstract: Peripheral neuropathy (PN), with neuropathic pain as main symptom, represents the dose-limiting toxicity of the proteasome inhibitor bortezomib. Aim of this study was to compare the incidence, risk factors, severity and outcome of PN and neuropathic pain in patient treated with bortezomib up-front or at relapse. We studied 55 patients with multiple myeloma (MM) who received bortezomib as first line therapy and 70 pre-treated patients who received bortezomib in relapse or progression. Regarding PN, no differences were found among untreated and pre-treated patients in the incidence (55% vs 52%, p=0.43), severity (NCI grade 3-4 9% vs 14%, p=0.27), and outcome (improved/resolved 90% vs 91%, p=0.58). Concerning neuropathic pain, the incidence was lower (50% vs 81%, p=0.008) and solved earlier (35 days vs 91 days, p=0.02) in untreated compared with pre-treated patients. Untreated patients needed dose modification less frequently (36% vs 73%, p=0.012). No correlation was found between development of PN and prior exposure to potentially neurotoxic drugs such as thalidomide, vincristine, and cysplatin. Age represented the main risk factor for PN (p=0.036) with an increase in risk of PN amounting to 6% per year of age. In conclusion, incidence, severity and outcome of bortezomib-related PN are similar in untreated and pre-treated MM patients except for neuropathic pain which has lower incidence and shorter duration in untreated patients with less frequent need for bortezomib discontinuation. Age emerges as the most relevant risk factor for peripheral neuropathy, with a risk increase for PN of 6% per year of age.
authors.affiliation: Division of Hematology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Viale Golgi 19, 27100 Pavia, Italy. a.corso@smatteo.pv.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Corso
authors.forename: Silvia
authors.initials: S
authors.lastname: Mangiacavalli
authors.forename: Marzia
authors.initials: M
authors.lastname: Varettoni
authors.forename: Cristana
authors.initials: C
authors.lastname: Pascutto
authors.forename: Patrizia
authors.initials: P
authors.lastname: Zappasodi
authors.forename: Mario
authors.initials: M
authors.lastname: Lazzarino
mesh_terms: D000203:Activities of Daily Living; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D000069286:Bortezomib; D017024:Chemotherapy, Adjuvant; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000453:epidemiology; D020360:Neoadjuvant Therapy; D009437:Neuralgia / Q000139:chemically induced / Q000209:etiology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000209:etiology; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D012307:Risk Factors
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib