A group of multiple myeloma experts from the International Myeloma Working Group recently published a review of management strategies for drug-induced peripheral neuropathy in patients with multiple myeloma.

This Beacon article, the second in a three-part series, summarizes the experts’ recommendations for the treatment of drug-induced peripheral neuropathy.

The first article ^[1] in the series describes peripheral neuropathy and summarizes the symptoms of drug-induced neuropathy as well as the risk of developing neuropathy associated with myeloma therapies.  A third article ^[2] will summarize the experts’ recommendations for prevention of peripheral neuropathy as well as future steps toward better management of the condition.

The authors of the International Myeloma Working Group review concede that there is limited data regarding the treatment of drug-induced peripheral neuropathy specifically in myeloma patients.

For this reason, drug dose reduction is currently the “gold standard” when it comes to helping myeloma patients with Velcade ^[3] (bortezomib)- or thalidomide ^[4] (Thalomid)-induced peripheral neuropathy.

Velcade

Based on the findings of several Phase 2 studies, dose-modification guidelines have been developed for the management of Velcade-induced peripheral neuropathy. These guidelines are also included in the prescribing information ^[5] for Velcade.

The guidelines state that patients who develop mild peripheral neuropathy without pain or loss of function should continue to receive the same dose of Velcade.

Patients who develop mild peripheral neuropathy with pain, or moderate peripheral neuropathy, should have their dose reduced to 1.0 mg/m² of Velcade.

Patients who develop moderate peripheral neuropathy with pain, or severe peripheral neuropathy, should discontinue Velcade until their condition improves. Then, they should begin to receive Velcade at a reduced dose of 0.7 mg/m² and once-weekly administration.

Patients with life-threatening peripheral neuropathy should discontinue Velcade.

In their review, the experts also agreed on a separate set of evidence-based dose modification guidelines for the management of Velcade-induced peripheral neuropathy.

“This is a proposed improvement on existing guidelines to reflect the role of combinations [of therapy] and the establishment of weekly Velcade as effective when indicated,” commented Dr. Paul Richardson of the Dana Farber Cancer Institute in Boston and the lead author of the review.

These consensus guidelines state that patients who develop mild or moderate peripheral neuropathy should receive Velcade either once per week or at a reduced dose. Patients who are already receiving Velcade once per week should further reduce their dose, or temporarily discontinue treatment and restart treatment at a reduced dose once their condition improves.

Patients who have moderate peripheral neuropathy with pain, severe peripheral neuropathy, or life-threatening peripheral neuropathy should discontinue Velcade.

In addition, the experts stated that patients may improve by switching from intravenous Velcade to subcutaneous Velcade.

“[Subcutaneous Velcade] is clearly less neurotoxic, reduces overall rates of peripheral neuropathy by 50 percent, and appears to be as effective as intravenous Velcade. However, it is not without its own challenges, including skin reactions,” said Dr. Richardson.

“Thus, strategies to reduce peripheral neuropathy with intravenous Velcade remain very important,” he added.

Thalidomide

Currently, there are no official dose modification guidelines for thalidomide-induced peripheral neuropathy.

For patients with mild peripheral neuropathy, the experts recommended cutting their thalidomide dose in half.

They further recommended that patients with moderate peripheral neuropathy discontinue treatment until their condition improves. Then, patients may restart with half of their original dose of thalidomide.

Based on current clinical practice, the experts noted that thalidomide should be discontinued in patients with severe or life-threatening peripheral neuropathy.

Other Treatment Measures

Several studies have shown positive results for the treatment of chemotherapy-induced peripheral neuropathy. However, these treatments have not yet been assessed in patients receiving anti-myeloma therapies.

According to the experts, anti-seizure medications such as gabapentin (Neurontin) and Lyrica (pregabalin) and anti-depression medications such as amitriptyline (Elavil) and Cymbalta (duloxetine) are commonly used for the treatment of drug-induced peripheral neuropathy.

Moreover, the amino acid acetyl-L-carnitine has shown activity in the treatment of drug-induced peripheral neuropathy.

Recent studies have also shown promising results for the treatment of drug-induced peripheral neuropathy with skin creams containing baclofen, amitriptyline, and ketamine.

Similarly, one study showed that menthol cream was effective in treating a patient with Velcade-induced nerve pain.

The experts warned that physicians who prescribe treatments for a myeloma patient with drug-induced peripheral neuropathy should keep in mind the patient’s current dosing schedule. The effectiveness of the potential treatments for peripheral neuropathy may be compromised if the patient continues to receive the same dose of neurotoxic anti-myeloma therapy.

For more information, please see the article in the journal Leukemia ^[6] (abstract).