title: Multiple myeloma: treatment evolution.
abstract: Melphalan-prednisone (MP) was introduced for the treatment of MM in late 1960s. In the subsequent 30 years, the treatment improvements remained stagnant, since more complex chemotherapy combinations, such as vincristine, doxorubicin, and dexamethasone (VAD),  or with the addition of BCNU (VBAD) or melphalan and cyclophosphamide (VCMP), only led to small increases in the overall response rate but without differences in survival, as assessed in a large meta-analysis that included over 6000 patients. The next step forward was the use of high-dose  melphalan followed by stem cell support (autologous stem cell transplant - ASCT) for young myeloma patients, which resulted in a significant improvement in disease free survival and overall survival. However, for elderly patients MP remained as the standard of care. From year 2000,  a revolution in the treatment armamentarium of MM has emerged with the availability of new agents with singular mechanism of action such as thalidomide and lenalidomide (Revlimid®), both immunomodulatory drugs and the proteasome inhibitor bortezomib (Velcade®).
authors.affiliation: Servicio de Hematología, Hospital Universitatio de Salamanca, CIC, IBMCC (USAL-CSIC), Spain. sanmigiz@usal.es
authors.forename: Jesus F
authors.initials: JF
authors.lastname: San Miguel
authors.forename: Maria Victoria
authors.initials: MV
authors.lastname: Mateos
authors.forename: Enrique
authors.initials: E
authors.lastname: Ocio
authors.forename: Ramón
authors.initials: R
authors.lastname: Garcia-Sanz
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000077269:Lenalidomide; D008558:Melphalan / Q000627:therapeutic use*; D009101:Multiple Myeloma / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000627:therapeutic use; D033581:Stem Cell Transplantation / Q000379:methods; D013792:Thalidomide / Q000031:analogs & derivatives / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D061988:Proteasome Inhibitors; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D000077269:Lenalidomide; D008558:Melphalan