Originally published as JCO Early Release 10.1200/JCO.2006.05.6689 on August 28 2006

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Development of Neuropathy in Patients With Myeloma Treated With Thalidomide: Patterns of Occurrence and the Role of Electrophysiologic Monitoring

Linda Mileshkin, Richard Stark, Bruce Day, John F. Seymour, Jerome B. Zeldis, H. Miles Prince

From the Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne; Department of Medicine, University of Melbourne, Melbourne; Department of Neurology, Alfred Hospital, Prahran; Department of Medicine, Monash University, Clayton, Australia; and the Celgene Corp, Warren, NJ

Address reprint requests to Linda Mileshkin, MBBS, Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne, Victoria 3002, Australia; e-mail: Linda.Mileshkin{at}petermac.org

PURPOSE: Peripheral neuropathy frequently limits the duration of treatment with thalidomide for patients with multiple myeloma. We assessed the time course of occurrence, possible predictive factors, and the utility of serial nerve electrophysiological studies (NES) for detecting onset of neuropathy.

PATIENTS AND METHODS: Seventy-five patients with relapsed/refractory myeloma were enrolled onto a multicenter trial of dose-escalating thalidomide with or without interferon. Patients underwent clinical assessment plus NES at baseline and every 3 months. Time to development of neuropathy according to clinical or NES criteria was compared. Patient and treatment-related factors were compared as predictors of neuropathy.

RESULTS: Thirty-nine percent had some NES abnormalities at baseline. Patients received thalidomide at a median dose-intensity of 373 mg/d. Thirty-one of 75 patients (41%) developed neuropathy during thalidomide treatment; 11 patients (15%) discontinued treatment with thalidomide due to neuropathy. The actuarial incidence of neuropathy increased from 38% at 6 months to 73% at 12 months, with 81% of responding patients developing this complication. Serial NES did not reliably predict the imminent development of clinical neuropathy requiring thalidomide cessation, nor were patient age, sex, or prior therapy predictive. Patients who developed neuropathy had a longer duration of thalidomide exposure (median, 268 v 89 days; P = .0001). Cumulative dose or dose-intensity received was not predictive.

CONCLUSION: The majority of patients will develop peripheral neuropathy given sufficient length of treatment with thalidomide. To minimize the risk of neurotoxicity, therapy should be limited to less than 6 months. Electrophysiologic monitoring provides no clear benefit versus careful clinical evaluation for the development of clinically significant neuropathy.

published online ahead of print at www.jco.org on August 28, 2006.

Supported by Celgene Corp, Warren, NJ, and by the Medical Oncology Group (Australia)/Novartis Clinical Research Fellowship (L.M.).

Presented in part at the 42nd Annual Meeting of the Americal Society of Clinical Oncology, Atlanta, GA, June 2-6, 2006.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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