For multiple myeloma patients, treatment history and personal predisposition have been identified as two key factors that may predict if a patient treated with Velcade ^[1] (bortezomib) or thalidomide ^[2] (Thalomid) will develop tingling and pain from nerve damage in their limbs.

Thalidomide and Velcade are among the many myeloma treatments that are neurotoxic, which means that they cause damage to the body’s nervous system. As a result, multiple myeloma patients commonly experience tingling and pain from nerve damage in their extremities as a side effect of treatment – this is called peripheral neuropathy, or peripheral nerve damage.

After reviewing numerous studies, researchers identified the characteristics of and differences between peripheral neuropathy induced by thalidomide and Velcade.

In patients treated with thalidomide, the risk of developing nerve damage in the limbs increased the longer they were exposed to the drug. In one study, patients who experienced peripheral neuropathy had received thalidomide for an average of about nine months, while patients who did not develop nerve damage were more likely to have received thalidomide for only about three months. Additionally, patients who receive thalidomide treatment for a year have a 70 percent chance of developing nerve damage. As a result, some of the studies recommended that patients be given thalidomide for no more than six months.

Thalidomide-based neuropathy often initially develops as stinging or numbness in the toes or sometimes the fingers, and then it spreads up the legs and arms. Patients may also experience trembling.

With Velcade, neuropathy is less common than with thalidomide. About 40 percent of patients receiving Velcade develop nerve dysfunction. However, patients typically developed it within the first few cycles of treatment, indicating that prolonged exposure to the drug is not the main cause of the nerve damage. Patients often feel pain, tingling, burning, or numbness in their feet rather than in their hands.

Researchers identified two key indicators for developing Velcade-induced peripheral neuropathy: treatment history and personal predisposition. They observed that patients who had received other neurotoxins like vincristine ^[3] (Oncovin) or cisplatin in the past were more susceptible to nerve damage when treated with Velcade. Also, patients who had pre-existing nerve damage caused directly by their multiple myeloma were more likely to experience Velcade-induced peripheral neuropathy.

Velcade-related neuropathy can be reversed or alleviated by reducing the dosage given. Therefore, researchers recommended fast, simple, and accurate testing to identify when patients develop nerve dysfunction so that they can develop a treatment plan instead of completely discontinuing Velcade. They also noted that weekly Velcade infusions may alleviate nerve damage better than the current standard of biweekly infusions.

Other than the duration of treatment, no other indicators were identified as able to predict thalidomide-induced peripheral neuropathy. The authors concluded, however, that physicians must quickly reduce or stop thalidomide treatment in patients who develop tingling because (unlike Velcade-induced neuropathy) nerve damage caused by thalidomide has the tendency to become irreversible. Doctors are also advised to closely monitor their patients’ diabetes and vitamin B12 levels, since both are general risk factors for peripheral neuropathy.

For the general treatment of peripheral neuropathy, the review authors proposed Lyrica (pregabalin) or gabapentin (Neurontin) as a first line treatment, followed by Cymbalta (duloxetine) as a second line treatment. They also recommended tramadol (Ultram) for pain relief.

They also offered practical suggestions to help alleviate the discomfort, such as wearing loose socks and shoes or padded slippers; uncovering one’s feet in bed; walking to stimulate blood circulation; and soaking or massaging one’s feet in icy water.

For more information, please see the full review published in the journal Haematologica ^[4].