In a recent Phase 3 trial, a Velcade ^[1] (bortezomib) and dexamethasone ^[2] (Decadron) combination resulted in the longest progression-free survival in multiple myeloma patients, including those at high risk. The study will be presented at the upcoming American Society of Hematology (ASH) meeting in New Orleans on Monday, December 7, 2009.

The trial compared the Velcade-dexamethasone combination (VD) with a vincristine ^[3], doxorubicin ^[4] (Adriamycin), and dexamethasone combination (VAD). As induction therapies, VD and VAD reduce the number of cancer cells in the body before a patient undergoes high-dose chemotherapy and autologous stem cell transplantation (HDT-ASCT).

In previous studies comparing the two treatments, a greater percentage of patients achieved at least very good partial response with VD induction. This trial examined the effects of VD and VAD induction therapies on progression-free survival.

Researchers randomly divided 482 patients into four treatment groups. Two groups of 121 patients each were treated with four 4-week cycles of VAD, one group with and one without dexamethasone, cyclophosphamide ^[5] (Cytoxan), etoposide (Eposin), and cisplatin (DCEP) consolidation chemotherapy. The other two groups (121 and 119 patients, respectively) were treated with four 3-week cycles of VD, with or without cisplatin.

Researchers also made sure to divide high risk patients evenly among each group. High risk patients were defined as either in Stage 3 or having cytogenetic, or chromosomal, abnormalities such as t(4;14) or del17p. Responses to VD and VAD induction therapies were evaluated before and after HDT-ASCT. Patients who did not achieve at least a very good partial response after the first autologous stem cell transplant could opt to undergo a second HDT-ASCT or an allogeneic stem cell transplant where stem cells are collected from a healthy donor. The median follow-up was 32.2 months.

Patients treated with VD experienced an average progression-free survival of 36 months, while patients treated with VAD averaged 29.7 months. In addition, patients who achieved at least a very good partial response before and after their first HDT-ASCT experienced a longer progression-free survival, regardless of their treatment group. This indicates that reducing the number of cancer cells in the body early in treatment greatly influences progression-free survival.

Additionally, high risk patients in the VD group did not experience a significantly shorter progression-free survival than other VD patients. This indicates that VD induction therapy may counter the poor prognosis associated with Stage 3 multiple myeloma and a genetic profile including t(4;14) or del17p.

For more information, see abstract 353 ^[6] at the ASH meeting Web site.