In multiple myeloma, autologous stem cell transplantation (ASCT) has been considered a standard of care in younger patients. The introduction of novel agents (i.e., thalidomide, lenalidomide, and bortezomib) may change this scenario. These agents can be administered before or after ASCT with the goal of increasing the complete remission (CR) rate and prolonging remission. For instance, thalidomide given as maintenance therapy after double ASCT increases CR rate, event-free survival (EFS), and overall survival. Moreover, combinations of conventional chemotherapy with novel agents such as thalidomide or bortezomib yield CR rates and EFS comparable to those achieved with standard single ASCT. Prospective randomized studies are needed to evaluate the impact of novel agents versus or in combination with ASCT. Myeloablative conditioning regimens before allogeneic stem cell transplantation are being replaced with concurrent autologous-transplantation and reduced-intensity conditioning allogeneic stem cell transplantation. Transplant-related mortality associated with this procedure is lower, but more follow-up is needed before definite conclusions can be drawn.
Jean-Luc Harousseau and Philippe Moreau
Edited by Kerrin G. Robinson
The introduction of novel agents (thalidomide, bortezomib, lenalidomide) is changing the management of patients with multiple myeloma who are candidates for stem cell transplantation. Bortezomib-dexamethasone given as induction treatment before autologous stem cell transplantation is significantly superior to the classical vincristine-doxorubicin-dexamethasone regimen in terms of complete response and very good partial response, both before and after transplantation. Triple combinations with thalidomide and bortezomib plus either cyclophosphamide or doxorubicin also yield excellent response rates, with the combination of bortezomib with thalidomide and dexamethasone seeming to be the most promising. Postautologous transplantation maintenance with thalidomide improves the response rate, progression-free survival, and, in some subgroups, overall survival. However, the optimal dose and duration of administration of thalidomide is not known. Both lenalidomide and bortezomib are being evaluated in this setting. The addition of novel agents before and after autotransplant yields a very high complete response rate and prolonged progression-free and overall survival. However, outstanding results have also been achieved with novel agents without transplantation. Therefore, randomized trials comparing novel agents with and without early transplantation are awaited. Tandem autologous plus reduced-intensity conditioning allogeneic transplantation have replaced myeloablative conditioning allogeneic transplantation. Despite improved results and decreased toxic death rate, this approach still carries the risk for morbidity and mortality related to graft-versus-host disease and should not be proposed in front-line therapy, especially in patients with no adverse prognostic features.