Features and risk factors of peripheral neuropathy during treatment with bortezomib for advanced multiple myeloma

Background: Bortezomib is a first-in-class proteasome inhibitor with remarkable antitumor activity that is approved for the treatment of patients with multiple myeloma. Peripheral neuropathy (PN) is a frequent adverse event reported with bortezomib use. Patients and Methods: The aim of this retrospective, single-center study was to determine the characteristics of bortezornib-associated PN in 100 patients with advanced myeloma. Peripheral neuropathy was evaluated by investgator's assessment. Results: With a median follow-up of 8 months (range, 0.1-32 months) from bortezomib initiation, bortezornib-associated PN was observed in 38 patients (38%; 95% CI, 28%-47%), with grade 3 and 4 PN occurring in 5 patients and 1 patient, respectively. Median time to onset of bortezornib-associated PN was 53 days (range, 11-182 days). Of the 38 patients with bortezomib-associated PN, resolution or improvement occurred in 20 patients (53%) at a median of 3 months (range, 1-8 months). In multivariate analysis, the total number of cycles of bortezomib (< 4 cycles or > 4 cycles; P=.03; odds ratio [OR], 2.6; 95% CI, 1.1-6.1) and a previous history of thalidomide therapy (P=.02; OR5 3.9; 95% CI, 1.212.6) were significantly associated with an increased incidence of bortezomib-associated PN. Conclusion: We conclude that, though relatively frequent, bortezomib-associated PN is reversible in a majority of patents. However, bortezomib-associated PN seems to be dependent on previous therapy with thalidomide, suggesting that bortezomib followed by thalidomide could be an optimal sequence of administration of these drugs in the salvage setting.