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.


METHODS
The aim of this retrospective, single-center study was to determine the characteristics of bortezomib-associated PN in 100 patients with advanced myeloma. Peripheral neuropathy was evaluated by investigator's assessment.


RESULTS
With a median follow-up of 8 months (range, 0.1-32 months) from bortezomib initiation, bortezomib-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 bortezomib-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; OR, 3.9; 95% CI, 1.2-12.6) were significantly associated with an increased incidence of bortezomib-associated PN.


CONCLUSIONS
We conclude that, though relatively frequent, bortezomib-associated PN is reversible in a majority of patients. 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.
El-Cheikh
Jean
J
Unité de Transplantation et de Thérapie Cellulaire, Institut Paoli-Calmettes, Marseille, France.
Stoppa
Anne-Marie
AM
Bouabdallah
Réda
R
de Lavallade
Hugues
H
Coso
Diane
D
de Collela
Jean-Marc Schiano
JM
Auran-Schleinitz
Thérèse
T
Gastaut
Jean-Albert
JA
Blaise
Didier
D
Mohty
Mohamad
M
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects*; D000069286:Bortezomib; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications* / Q000201:enzymology / Q000401:mortality* / Q000628:therapy; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000401:mortality*; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies; D012307:Risk Factors; D016879:Salvage Therapy / Q000009:adverse effects; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects
D000970:Antineoplastic Agents; D001897:Boronic Acids; D007166:Immunosuppressive Agents; D061988:Proteasome Inhibitors; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib