Novel agents, such as Velcade ^[1] (bortezomib) and Revlimid ^[2] (lenalidomide), have greatly advanced the treatment of patients with multiple myeloma. Indeed, by incorporating novel agents as induction therapy prior to consolidation with high-dose therapy and autologous stem cell transplantation, we have made huge strides in survival outcomes over the last 10 years.  However, treatment with anti-myeloma agents may be associated with side effects that negatively impact quality of life.

Recently, two advances have been reported resulting in a decrease in peripheral neuropathy (nerve damage causing pain, numbness, and/or tingling in the extremities) for patients receiving Velcade.

A report ^[3] by the Italian group compared once weekly Velcade with twice weekly Velcade. They observed similar response rates and survival between the two groups – predominantly because the twice weekly group had dose reductions or discontinued therapy due to side effects that were not nearly as evident with the once weekly schedule (15 percent versus 5 percent).  Further, more severe peripheral neuropathy was reduced from 28 percent to 8 percent.  (See related Beacon ^[4] news for more information.)

In a second trial ^[5] reported by the French Myeloma Intergroup, they utilized subcutaneous Velcade injections (just under the skin) rather than the standard intravenous infusions. Again, response rates and duration of response were virtually identical between the two methods of Velcade administration.  However, side effects were significantly less apparent in the group of patients administered subcutaneous Velcade: moderate neuropathy decreased from 41 percent to 24 percent and severe neuropathy from 16 percent to 6 percent. (See related Beacon ^[6] news for more information.)

In the Myeloma Division at The John Theurer Cancer Center at Hackensack University Medical Center, we have incorporated the subcutaneous administration of Velcade for all of our patients. Only a single patient has requested to be converted back to intravenous administration due to localized rash at the injection site. Whereas most patients continue to receive twice weekly Velcade, a number of our patients are treated with once weekly Velcade depending upon the individual patient’s clinical status.

Revlimid, a novel immunomodulatory agent, does not cause nerve damage as one of its side effects. However, one of the limitations to using Revlimid is related to its renal (kidney) clearance. Approximately 20 percent of myeloma patients have some degree of abnormal kidney function. In patients with abnormal kidney function, Revlimid remains in the body longer and may cause bone marrow suppression. These patients have lower blood counts, which may be associated with infections (low white counts), anemia (low red counts) or bleeding risks (low platelet counts).

In a recent study ^[7], Revlimid was administered to people without myeloma who had varying degrees of kidney failure to determine an acceptable dosing schedule. These results have been incorporated into treatment guidelines ^[8] allowing for the safe treatment of myeloma patients with Revlimid.

In summary, we have established safer treatment approaches with the two most active agents for the treatment of myeloma.  These modifications of prior administration schedules for Velcade and Revlimid will allow us to maintain excellent responses and improve survival while decreasing the side effects associated with these treatments.  This is a win-win situation – longer remissions, longer survival, and improved quality of life!

Dr. David H. Vesole is Co-Chief of the Myeloma Division and Director of Myeloma Research at The John Theurer Cancer Center at Hackensack University Medical Center. Dr. Vesole writes a quarterly column for The Myeloma Beacon.