At the recent American Society of Hematology (ASH) annual meeting, there were several presentations comparing a drug regimen of Velcade ^[1] (bortezomib), thalidomide ^[2] (Thalomid), and dexamethasone ^[3] (Decadron), abbreviated as VTD, with a drug regimen of thalidomide and dexamethasone, abbreviated as TD, in newly diagnosed multiple myeloma patients.

Update: VTD Versus TD With Double Autologous Stem Cell Transplantation

One of the ASH presentations showed that the addition of Velcade to a thalidomide-dexamethasone regimen and double autologous stem cell transplantation significantly improves the response rate in newly diagnosed multiple myeloma patients. The presentation on the recent Phase 3 clinical trial updated the Phase 2 clinical trial results ^[4] reported at the 2008 ASH meeting.

Patients were randomly assigned to receive three 21-day cycles of either VTD or TD.  Patients receiving the VTD regimen were given 1.3 mg/m² of Velcade twice-weekly, 200 mg of thalidomide daily, and 320 mg/cycle of dexamethasone. Patients receiving the TD regimen were given thalidomide and dexamethasone at the same dose and schedule as in the VTD regimen.

Following treatment with either VTD or TD, patients underwent two sequential autologous stem cell transplantations, which is commonly known as a double autologous stem cell transplantation. The procedure uses stem cells collected prior to chemotherapy to replace any cells damaged during the chemotherapy treatment. All patients later received two 35-day cycles of either VTD or TD as consolidation therapy.

Researchers found that patients treated with three cycles of VTD prior to double stem cell transplantation had higher rates of very good partial response or better than those treated with TD – 62 percent versus 31 percent; including a complete response of 19 percent versus 5 percent. These rates remain consistent with those found in the Phase 2 clinical trial.

Importantly, no patient receiving the VTD regimen experienced disease progression, compared to five percent of patients treated with TD. An update at the ASH meeting showed that the two-year projected progression-free survival for VTD treated patients was 85 percent compared to 75 percent of TD treated patients. However, longer follow-up is needed to determine if there is a difference in overall survival rate for the two treatments.

Low-Dose VTD Versus VD With Single Autologous Stem Cell Transplantation

Results from another study presented at ASH show that reduced doses of Velcade and thalidomide in the VTD regimen (followed by a single autologous stem cell transplantation) significantly increase rates of complete response and very good partial response.

Noting that peripheral neuropathy (a form of nerve damage in the extremities that can cause pain and tingling sensations) was the most common side effect of the VTD regimen, the authors of this study examined if decreased doses of Velcade and thalidomide could minimize the frequency of this adverse effect. Patients were randomly assigned to receive either low-dose VTD or standard-dose VD for four 21-day cycles.

Patients assigned to receive VD were given 1.3 mg/m² of Velcade on days 1, 4, 8, and 11, in addition to 40 mg of dexamethasone on days 1 to 4 and 8 to 11 for the first two cycles and on days 1 to 4 for the last two cycles. Patients assigned to receive low-dose VTD were given 1 mg/m² of Velcade on days 1, 4, 8, and 11; 100 mg of thalidomide daily; and dexamethasone, in the same dose and schedule as for VD.

Researchers found that patients treated with four cycles of low-dose VTD prior to stem cell transplantation had higher partial rates of response or better than those treated with VD – 91 percent versus 81 percent; including a complete response of 14 percent versus 12 percent and a very good partial response of 50 percent versus 36 percent. Importantly, the frequency of peripheral neuropathy was significantly reduced, with only two percent of patients receiving VTD experiencing serious peripheral neuropathy.

Based on these results, the authors of the study concluded that low-dose VTD should be considered as a new standard treatment to be given prior to autologous stem cell transplantation.

For more information, see abstracts 351 ^[5] (VTD versus TD), and 354 ^[6] (VTD versus VD) at the ASH meeting Web site.