title: Early or delayed transplantation for multiple myeloma in the era of novel therapy: does one size fit all?
abstract: For the last 20 years, high-dose therapy with autologous stem cell transplantation (ASCT) for multiple myeloma has been considered a standard frontline treatment for younger patients with adequate organ function. With the introduction of novel agents, specifically thalidomide, bortezomib, and lenalidomide, the role of ASCT has changed in several ways. First, novel agents have been incorporated successfully as induction regimens, increasing the response rate before ASCT, and are now being used as part of both consolidation and maintenance with the goal of extending progression-free and overall survival. These approaches have shown considerable promise with significant improvements in outcome. Furthermore, the efficacy of novel therapeutics has also led to the investigation of these agents upfront without the immediate application of ASCT, and compelling preliminary results have been reported. Next-generation novel agents and the use of monoclonal antibodies have raised the possibility of not only successful salvage strategies to facilitate delayed transplantation for younger patients, but also the prospect of an nontransplantation approach achieving the same outcome. Moreover, this could be achieved without incurring acute toxicity or long-term complications that are inherent to high-dose alkylation, and melphalan exposure in particular. At present, the role of ASCT has therefore become an area of debate: should it be used upfront in all eligible patients, or should it be used as a salvage treatment at the time of progression for patients achieving a high quality of response with initial therapy? There is a clear need to derive a consensus that is useful for clinicians considering both protocol-directed and non-protocol-directed options for their patients. Participation in ongoing prospective randomized trials is considered vital. While preliminary randomized data from studies in Europe favor early ASCT with novel agents, differences in both agents and the combinations used, as well as limited information on overall survival and benefit for specific patient subsets, suggest that one size does not fit all. Specifically, the optimal approach to treatment of younger patients eligible for ASCT remains a key area for further research. A rigid approach to its use outside of a clinical study is difficult to justify and participation in prospective studies should be a priority.
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Laubach
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Nikhil C
authors.initials: NC
authors.lastname: Munshi
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007167:Immunotherapy; D009101:Multiple Myeloma / Q000188:drug therapy / Q000628:therapy; D012074:Remission Induction; D014182:Transplantation, Autologous
chemical_list: D000970:Antineoplastic Agents