Bortezomib/dexamethasone versus VAD as Induction Prior to Autologous Stem Cell Transplant (ASCT) in Previously Untreated Multiple Myeloma (MM): Updated Data from IFM 2005/01 Trial
The use of autologous stem cell transplant in treating multiple myeloma patients over 65 years of age has become standard therapy. Traditionally, the VAD chemotherapy regimen was used as first line induction therapy. This study looked at using bortezomib and dexamethasone (BD) as induction therapy, compared with VAD. This was based on the theory that both bortezomib and dexamethasone inhibit different peptides, resulting in a blockade of important cell pathways that are necessary for growth and replication. It is hoped that this interference will lead to greater cell death.
Patients were randomly assigned to one of the following therapies:
BD alone (4 cycles), VAD alone (4 cycles), BD followed by consolidation therapy with 2 cycles of dexamethasone, cyclophosphamide, etoposide, and platinum (DCEP), or VAD followed by 2 cycles of DCEP. 442 patients were evaluated.
BD had superior response rates in low-, intermediate-, and high-risk patients. Patients with high and low levels of beta2 microglobulin and patients with and without deletion of chromosome 13 all benefited from BD therapy. The responses were classified as complete and near complete (8.3% in VAD arm vs. 21.3% in BD arm) and "more than a very good partial response" (18.6% in the VAD arm vs. 46.7% in the BD arm). These patients went on to have stem cell transplants, and the superior response in the BD arm was still present after transplant. The addition of DCEP did not increase response rates. The BD superiority did not translate into improved survival rates at 18 months, but longer follow up is needed.
Side effects varied, with neuropathy and thrombocytopenia being higher in the BD arm and neutropenia and anemia being higher in the VAD arm.
Although this study does suggest great potential for this induction therapy regimen, it is not yet the standard of care. Longer follow-up is needed, and there should ideally be a true improvement in quality of life, overall survival, and/or cost of treatment (with equivalence of effect) prior to accepting this regimen as the standard of care for induction prior to ASCT.