Integrating novel therapies in the transplant paradigm.

The introduction of novel therapies (thalidomide, bortezomib, and lenalidomide) is changing the management of multiple myeloma in younger patients who are usually candidates for autologous stem cell transplantation (ASCT). Randomized trials have shown the superiority of induction treatment with novel agents compared with the classic VAD regimen. Complete remission plus very good partial remission rates of 40% to 60% after induction and of 60% to 75% are achieved with bortezomib-dexamethasone or with 3-drug combinations (including 1 or 2 novel agents). Six randomized studies have evaluated the impact of thalidomide as post-ASCT maintenance therapy. Despite differences in the design of the studies and in thalidomide administration, all 6 studies show a significant benefit in the thalidomide arm in terms of response rate and progression-free survival. Results are not as clear in terms of survival. The addition of novel agents before and after ASCT yields very high complete remission and promising progression-free survival rates. On the other hand, results obtained with novel agents are attractive as well and randomized studies comparing novel agents plus early ASCT versus novel agents plus ASCT at progression are planned.