title: Neuropathy and efficacy of once weekly subcutaneous bortezomib in multiple myeloma and light chain (AL) amyloidosis.
abstract: BACKGROUND
  Randomized studies have shown that bortezomib (BTZ) can be given weekly via intravenous (IV) route or twice weekly via subcutaneous (SC) route with lower neuropathy risk and no loss of anti-myeloma efficacy compared to original standard IV twice weekly schedule. Weekly SC should therefore yield the best therapeutic index and is widely used but has not been compared to established administration schedules in the context of a clinical trial.
  
  
  METHODS
  Comprehensive electronic medical record review was done for disease control and neuropathy symptoms of 344 consecutive patients who received their first BTZ-containing regimen for myeloma or AL amyloidosis before or after we changed to SC weekly in December 2010. Univariate and multivariable analyses were carried out that adjusted for age, underlying disease, concurrently used anticancer agents, underlying conditions predisposing to neuropathy, and number of prior regimens compared SC weekly to other schedules.
  
  
  RESULTS
  Fifty-three patients received BTZ SC weekly, 17 SC twice weekly, 127 IV weekly and 147 IV twice weekly. Risk for neuropathy of any grade was higher with other schedules compared to SC weekly (44.3% vs. 26.9%, p = 0.001) while response rate was similar (72.1% vs. 76.6%, respectively, p = 0.15). Multivariable analyses upheld higher neuropathy risk (Odds ratio 2.45, 95% CI 1.26-4.76, p = 0.008) while the likelihood of not achieving a response (= partial response or better) was comparable (Odds ratio 1.25, 95% CI 0.58-2.71, p = 0.56) for other schedules compared to SC weekly, respectively. Lower neuropathy risk translated into longer treatment duration when BTZ was started SC weekly (p = 0.001).
  
  
  CONCLUSIONS
  Weekly SC BTZ has activity comparable to other schedules and causes low rates of neuropathy.
authors.affiliation: Department of Internal Medicine, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Surbhi
authors.initials: S
authors.lastname: Sidana
authors.affiliation: Department of Internal Medicine, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Mayur
authors.initials: M
authors.lastname: Narkhede
authors.affiliation: Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Paul
authors.initials: P
authors.lastname: Elson
authors.affiliation: Department of Cancer Center Research, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Debbie
authors.initials: D
authors.lastname: Hastings
authors.affiliation: Department of Hematology & Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Beth
authors.initials: B
authors.lastname: Faiman
authors.affiliation: Department of Hematology & Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Jason
authors.initials: J
authors.lastname: Valent
authors.affiliation: Department of Hematology & Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Christy
authors.initials: C
authors.lastname: Samaras
authors.affiliation: Department of Hematology & Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Hamilton
authors.affiliation: Department of Hematology & Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Hien K
authors.initials: HK
authors.lastname: Liu
authors.affiliation: Department of Hematology & Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Mitchell R
authors.initials: MR
authors.lastname: Smith
authors.affiliation: Department of Hematology & Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Frederic J
authors.initials: FJ
authors.lastname: Reu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000686:Amyloidosis / Q000150:complications / Q000188:drug therapy*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000069286:Bortezomib / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy*; D015999:Multivariate Analysis; D016017:Odds Ratio; D010523:Peripheral Nervous System Diseases / Q000517:prevention & control*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000069286:Bortezomib