Treatment of multiple myeloma in the targeted therapy era.
OBJECTIVE
To review the clinical trials that have impacted treatment standards of multiple myeloma (MM).


METHODS
A PubMed search (1980-June 2008) restricted to English-language publications was conducted using the key words multiple myeloma, clinical trials, targeted therapy, thalidomide, lenalidomide, bortezomib, dexamethasone, melphalan, autologous stem-cell transplantation, and tumor biology. Abstracts emanating from the meetings of the American Society of Clinical Oncology and American Society of Hematology from June 2002 to June 2008 were also reviewed.


RESULTS
Although hematopoietic stem-cell transplantation has improved the response rate and duration of overall survival, MM remains an incurable disease. However, focused research aimed at the molecular basis of the disease has led to a number of new treatment strategies. Evidence from clinical trials indicates that each of the 3 novel agents, thalidomide, lenalidomide, and bortezomib, is remarkably effective as first-line therapy. The data also suggest that clinicians may need to reevaluate the role of stem-cell transplantation in the disease.


CONCLUSIONS
Thalidomide, lenalidomide, or bortezomib in combination with dexamethasone have replaced traditional chemotherapy such as melphalan, doxorubicin, and vincristine as initial therapy of patients with MM who are eligible for stem-cell transplantation. Furthermore, these novel drugs can be incorporated into regimens used to treat transplant-ineligible patients or those with relapsing disease.
Saad
Ayman A
AA
Section of Neoplastic Diseases and Related Disorders, Department of Internal Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
Sharma
Manish
M
Higa
Gerald M
GM
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001897:Boronic Acids / Q000008:administration & dosage*; D000069286:Bortezomib; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D003907:Dexamethasone / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000077269:Lenalidomide; D008558:Melphalan / Q000627:therapeutic use; D009101:Multiple Myeloma / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D011239:Prednisolone / Q000627:therapeutic use; D011719:Pyrazines / Q000008:administration & dosage*; D016879:Salvage Therapy; D013792:Thalidomide / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D019172:Transplantation Conditioning
D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D011239:Prednisolone; D000077269:Lenalidomide; D008558:Melphalan