An international group of myeloma researchers has recently identified five genetic variations that may be associated with an increased risk of developing thalidomide-related peripheral neuropathy. Several of these genes are involved in repairing nerves or controlling inflammation in the peripheral nervous system.
The researchers indicated that these genetic variations may be a tool to help identify patients who are at a greater risk of developing thalidomide-related peripheral neuropathy.
However, the researchers pointed out that their findings were based on data from patients who received intermediate doses of thalidomide and who developed the side effect early in the treatment cycle. Patients who developed neuropathy after prolonged exposure to thalidomide were not included in the analysis.
Thalidomide (Thalomid) is one of the three novel agents that has significantly improved survival of multiple myeloma patients.
However, the benefits of thalidomide are sometimes limited by the onset of several side effects, including peripheral neuropathy. Peripheral neuropathy causes pain and tingling in the arms, legs, hands, and feet.
Previous research has shown that depending on thalidomide dosage and duration of therapy, 15 to 70 percent of patients may experience peripheral neuropathy after thalidomide treatment.
Although it has been speculated that genetic factors may influence the risk of developing thalidomide-related peripheral neuropathy, there is limited research available on the topic.
In order to determine these genetic factors, the researchers analyzed the genetic variations of patients from two large European clinical trials who had received thalidomide- or vincristine (Oncovin)-based treatments.
For patients treated with thalidomide, 31.8 percent developed neuropathy. For patients treated with vincristine, 33.6 percent developed neuropathy. The median time to onset of neuropathy was eight weeks in both sets of patients. By comparison, only 6.4 percent of patients who did not receive thalidomide or vincristine developed neuropathy.
In order to determine the role of genetic factors in the development of neuropathy, researchers compared the genetic variations between patients who developed neuropathy and those who did not.
Researchers identified variations in five different genes that were associated with a high risk of thalidomide-related peripheral neuropathy.
Following these findings, researchers determined the function of these genes. Several of the genes were directly responsible for the development, inflammation, and repair mechanisms of the central and peripheral nervous system, which may explain why they are associated with neuropathy.
Researchers also found little overlap in the genes associated with thalidomide-related and vincristine-related peripheral neuropathy, which suggests that the mechanisms leading to the two neuropathies are fundamentally different.
For more information about the study or the specific genetic variations associated with thalidomide-related neuropathy, please see the Journal of Clinical Oncology (abstract).