Managing treatment-related peripheral neuropathy in patients with multiple myeloma

Abstract

Peripheral neuropathy is one of the most important complications of multiple myeloma treatment. Neurological damage can be observed at the onset of the disease, due to the effect of monoclonal protein or radicular compression, but more often is treatment related. Vinca alkaloids in the past era, and more recently, thalidomide and bortezomib are mainly responsible. Degeneration of dorsal root ganglion is common, prevalently related to angiogenesis inhibition and cytokine modulation in the case of thalidomide and inhibition of the ubiquitin proteasome system in the case of bortezomib. Sensory neuropathy and neuropathic pain are more common; motor neuropathy and autonomic damage are less frequently observed. Neurotoxicity often affects patient's quality of life and requires dose modification or withdrawal of therapy, with a possible effect on the overall response. A prompt recognition of predisposing factors (such as diabetes mellitus, alcohol abuse, vitamin deficiencies, or viral infections) and appearance of signs and symptoms, through a periodic neurological assessment with appropriate scales, is extremely important. Effective management of treatment at the emergence of peripheral neuropathy can minimize the incidence and severity of this complication and preserve therapeutic efficacy. Dose adjustment could be necessary during treatment; moreover, gabapentin or pregabalin, tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, carbamazepine, and opioid-type analgesics are suggested according to the pain severity. Some authors reported that patients who develop peripheral neuropathy during their multiple myeloma treatments presented a particular gene expression profile; therefore, future studies could be helpful for a better understanding of possible biological pathways underlying neurotoxicity.

Keywords: bortezomib-induced peripheral neuropathy; neurotoxicity; thalidomide-induced peripheral neuropathy.

Figure 1

Principal mechanisms of neuronal damage induced by bortezomib: ubiquitinated protein accumulated in the cytoplasm with production of aggresomes, endoplasmic reticulum stress, mitochondria dysfunction, axonal transport damage due to mitotoxicity and cytoskeleton alteration, DNA damage, and dysregulation of cytokines.