Results from a new study indicate that, in elderly multiple myeloma patients, a combination drug regimen of Velcade (bortezomib), melphalan (Alkeran), prednisone, and thalidomide (Thalomid) (VMPT), followed by a maintenance regimen of Velcade and thalidomide, is superior to the current standard treatment of Velcade, melphalan, and prednisone (VMP) without a maintenance regimen. The authors of the study will be presenting the results of the Phase 3 clinical trial at the upcoming American Society of Hematology (ASH) Annual Meeting and Exposition.

In the study, scientists randomly assigned 511 myeloma patients older than 65 years to receive either VMPT treatment, followed by maintenance with Velcade and thalidomide, or VMP treatment without maintenance. Treatment for both combinations initially lasted for nine 6-week cycles.

Patients assigned VMPT were administered 1.3 mg/m² of Velcade on days 1, 4, 8, 11, 22, 25, 29, and 32 in the first four cycles and on days 1, 8, 22, and 29 in the last five cycles; 9 mg/m² of melphalan on days 1 to 4; 60 mg/m² prednisone on days 1 to 4; and 50 mg of thalidomide on days 1 to 42. Patients also received 1.3 mg/m² of Velcade every 15 days and 50 mg of thalidomide every day as part of the maintenance regimen. Patients assigned VMP were given Velcade, melphalan, and prednisone at the same doses and schedules as those receiving VMPT. However, patients did not receive maintenance therapy with Velcade and thalidomide.

This protocol was amended in March 2007 for patients to receive nine 5-week cycles of treatment instead. The dosing schedule of Velcade was also modified to doses of 1.3 mg/m² on days 1, 8, 15, and 22.

Analysis of the trial results indicated that the response rates for the VMPT treatment were superior to those of the VMP treatment. For patients receiving VMPT, 86 percent achieved a partial response, compared to 79 percent of those patients receiving VMP. Fifty-five percent of patients receiving VMPT achieved a very good partial response, compared to 47 percent of patients receiving VMP. Thirty-four percent of patients receiving VMPT achieved a complete response, compared to 21 percent of patients receiving VMP.

However, patients receiving VMPT had a higher incidence of neutropenia (low white blood cell count) and cardiac complications than those patients receiving VMP. The frequency of side effects deemed serious and potentially life threatening was similar for patients in the VMPT group and in the VMP group. These side effects included decreased platelet count, peripheral neuropathy (nerve damage in the extremities that can cause pain and tingling sensations), infections, and gastrointestinal complications. The authors of the study noted that the modification in the dosing protocol from biweekly to weekly Velcade treatments significantly decreased the frequency of serious complications in patients in the VMPT group.

The authors of the study concluded that VMPT treatment, followed by maintenance with Velcade and thalidomide, produced superior response rates to VMP treatment without maintenance. This is the first study to demonstrate the superiority of the four-drug regimen, compared to the standard VMP treatment.

For more information, see abstract 128 at the ASH meeting Web site.