Clinical Characteristics and Predictive Factors of Peripheral Neurophaty in Multiple Myeloma Patients Treated with Bortezomib and/or Imids

Peripheral neuropathy (PN) and neuropathic pain are common and severe dose-limiting side effects of Bortezomib and/or IMIDs used in the management of multiple myeloma patients, which often requires dose reduction or interruption of treatment.

We performed a monocentric prospective study to investigate the incidence, clinical characteristics and predictive factors of peripheral neuropathy and neuropathic pain in multiple myeloma patients treated with Bortezomib and/or IMIDs.

All patients underwent clinical examination and were studied for the standard nerve conduction using the sural nerve action potential (SAP) trend. Neurological evaluation was performed monthly before, during and after Bortezomib and/or IMIDs treatment. Neuropathic pain was evaluated using the Douleur Neuropathique 4 (DN4) questionnaire and the Total Neuropathy Score reduced version.

Between January 2007 and June 2011, 145 consecutive patients, treated with Bortezomib and/or IMIDs, were prospectively studied. The clinical characteristics were: median age 60 years (range 32–78); 68 men and 77 women; 80 and 65 patients were, respectively, in Durie and Salmon stages I-II and III. Fifty-eight patients (40%) were treated with Bortezomib, 20 (14%) with Thalidomide, 37 (26%) with Lenalidomide and 30 (20%) with the Bortezomib-Thalidomide combination. After a median time of 3 months (range 1–22) from the start of our study, 100 patients (69%) developed a peripheral neuropathy during treatment; 78 (54%) patients had pain according to the DN4 questionnaire and 45 (31%) experienced neuropathic pain according to the Total Neuropathy Score. A significant difference (p<0.01) in terms of age and median time from diagnosis to the neurological examination was observed between patients with and without peripheral neuropathy. Patients with peripheral neuropathy were older and had a longer median time from diagnosis to the neurological examination: median age 59 vs 43 years (range 45–78 vs 32–62) and 45 vs 22 months (range 1–160 vs 1–36) from diagnosis. In addition, the different treatments were significantly associated with the development of peripheral neuropathy: the Bortezomib-Thalidomide combination and Bortezomib or Thalidomide alone were more frequently associated with peripheral neuropathy than Lenalidomide (p<0.05). No correlation between PN occurrence and cumulative dose of Bortezomib and IMIDs was observed. Among 30 patients (20%) treated with the Bortezomib-Thalidomide combination as first line of therapy, 22 (72%) experienced a peripheral neuropathy. In this group of patients, according to the SAP study, the neuropathy appeared after a median of 1.6 months of treatment and worsened after 3 months (Fig. 1). Sixteen patients continued Bortezomib-Thalidomide at the same dosage and 6 patients required a Bortezomib-Thalidomide dose reduction. An improvement of the neuropathy was observed after 4 months from the stop of treatment.

Our data underline the clinical importance of peripheral neuropathy and pain in patients with multiple myeloma. Age, duration of disease and treatment are predictive factors of peripheral neuropathy development. The Douleur Neuropathique 4 (DN4) and Total Neuropathy Score questionnaires are useful tools to evaluate neuropathic pain. We also observed that a reduction of SAP occurs early in patients who developed a neuropathy that improves after the end of treatment. This finding could suggest the presence of biological factors predisposing to the development of neuropathy.

Fig.1

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Sural action potential (SAP) trend after 1, 3 and 6 months from the beginning of the Bortezomib-Thalidomide combination.

Fig.1

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Sural action potential (SAP) trend after 1, 3 and 6 months from the beginning of the Bortezomib-Thalidomide combination.

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Petrucci:Janssen, Celgene: Honoraria.