The combination treatment of reduced-dose Velcade (bortezomib), thalidomide (Thalomid), and dexamethasone (Decadron), abbreviated vTD, appears to be a safe and effective induction treatment for newly diagnosed multiple myeloma patients prior to stem cell transplantation.

The combination treatment yielded higher complete and partial remission rates, and fewer and less severe side effects, than treatment with standard dose Velcade plus dexamethasone (VD).

The vTD vs. VD findings were presented by Dr. Philippe Moreau of the University Hospital in Nantes, France, at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago last Sunday.

“The new treatment combination is superior to VD, with a very good efficacy/toxicity ratio,” said Dr. Moreau.

Determining an optimum drug combination and dosage for multiple myeloma treatments can be difficult and requires extensive and systematic research. Dr. Moreau and his colleagues had learned from previous clinical trials that the VD combination was more effective than the vincristine-doxorubicin (Adriamycin)-dexamethasone (VAD) combination, and that VTD treatment was more effective than thalidomide-dexamethasone (TD) treatment.

Given these results, Dr. Moreau and his colleagues decided it would be “very interesting to try to compare VD and VTD in a prospective randomized trial.”

Dr. Moreau’s team was motivated, as well, by the fact that many participants in previous trials experienced mild to severe side effects with both the VD and VTD combinations.  Nerve damage in the extremities – peripheral neuropathy – was particularly a problem.

In hopes of reducing those side effects, the researchers in this study altered the VTD combination by lowering Velcade’s dose from 1.3 to 1.0 mg/m² per day and thalidomide’s dose from 200 mg to 100 mg. The Velcade dose in the VD combination remained at 1.3 mg/m² per day of Velcade.

Of the 199 newly-diagnosed multiple myeloma patients who participated in this study, 100 received four 21-day cycles of the reduced-dose vTD drug combination, and 99 received four cycles of the VD drug combination.

Complete remission rates, very-good partial response rates, and partial response rates were determined for each group after two treatment cycles, after four treatment cycles, and after stem cell transplantation.

After two treatment cycles, the VD treatment yielded a 78 percent partial response rate. The vTD treatment yielded a 90 percent partial response rate, which, according to Dr. Moreau, is an indicator for a very rapid response.

After four cycles, the partial response rates were 81 percent and 90 percent for the VD and vTD groups, respectively.

The very-good partial response rates after four cycles for the VD and vTD groups were 35 percent and 51 percent. After stem cell transplantation, these rates increased to 59 percent and 73 percent for VD and vTD, respectively.

The complete remission rates for VD and vTD were 12 percent and 13 percent, respectively, after four cycles. The difference in complete remission rates were not as significant as the researchers hoped they would be. “The primary endpoint of the study, which was an improvement of the complete remission rate in the vTD arm, was not achieved,” said Dr. Moreau.

However, the marked increase in high very good partial response rates of vTD after induction therapy and after stem cell transplantation is promising, according to Dr. Moreau. “We know from previous studies that a very good response rate both after induction and after stem cell transplantation is a very important goal to achieve. It is clearly related to a better outcome for the patients.”

In addition to conferring a greater therapeutic benefit to participants, the vTD combination also caused less severe side effects. The side effect of greatest importance in this study was peripheral neuropathy. Dr. Moreau and his colleagues found that patients receiving the lower-dose vTD combination experienced less prevalent and less severe peripheral neuropathy than those receiving the VD combination.

Eighteen percent of patients in the vTD group experienced nerve damage to the extremities, compared to 34 percent of those in the VD group. “Our goal was to reduce the rate of peripheral neuropathy by using a lower dose of Velcade and a lower dose of thalidomide, and that goal was achieved,” said Dr. Moreau.

Dr. Moreau concluded that low-dose vTD treatment is more effective and safer than VD treatment, due to the higher response rates it elicited among participants both after induction therapy and after stem cell transplantation and due its reduced side effects. “Decreasing the dose of Velcade and thalidomide does not impair the efficacy of this combination,” added Dr. Moreau.

”This is excellent,” said Dr. Joseph Mikhael of the Mayo Clinic, Arizona. “This is moving us significantly further ahead in our understanding of the dosing of these agents.”

“The combination of an immunomodulatory drug (e.g., thalidomide) with Velcade is clearly a highly synergistic combination,” said Dr. Brian Durie of Cedars Sinai in Los Angeles and the International Myeloma Foundation.

For more information about this study, please refer to abstract 8014 on the ASCO meeting website.