Neuropathy and efficacy of once weekly subcutaneous bortezomib in multiple myeloma and light chain (AL) amyloidosis

PLoS One. 2017 Mar 9;12(3):e0172996. doi: 10.1371/journal.pone.0172996. eCollection 2017.

Abstract

Introduction: 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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amyloidosis / complications
  • Amyloidosis / drug therapy*
  • Antineoplastic Agents / therapeutic use*
  • Bortezomib / therapeutic use*
  • Drug Administration Schedule
  • Female
  • Humans
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Multiple Myeloma / complications
  • Multiple Myeloma / drug therapy*
  • Multivariate Analysis
  • Odds Ratio
  • Peripheral Nervous System Diseases / prevention & control*
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Bortezomib

Grant support

The authors received no specific funding for this work.