Treatment of multiple myeloma.
Autologous peripheral blood stem cell (PBSC)-supported high-dose melphalan is now considered standard therapy for myeloma, at least for younger patients. The markedly reduced toxicity of allotransplants using nonmyeloablative regimens (mini-allotransplantations) may hold promise for more widely exploiting the well-documented graft-versus-myeloma (GVM) effect. New active drugs include immunomodulatory agents, such as thalidomide and CC-5013 (Revimid; Celgene, Warren, NJ), and the proteasome inhibitor, PS 341 (Velcade; Millenium, Cambridge, MA), all of which not only target myeloma cells directly but also exert an indirect effect by suppressing growth and survival signals elaborated by the bone marrow microenvironment's interaction with myeloma cells. Among the prognostic factors evaluated, cytogenetic abnormalities (CAs), which are present in one third of patients with newly diagnosed disease, identify a particularly poor prognosis subgroup with a median survival not exceeding 2 to 3 years. By contrast, in the absence of CAs, 4-year survival rates of 80% to 90% can be obtained with tandem autotransplantations. Fundamental and clinical research should, therefore, focus on the molecular and biologic mechanisms of treatment failure in the high-risk subgroup.
Barlogie
Bart
B
Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. barlogiebart@uams.edu
Shaughnessy
John
J
Tricot
Guido
G
Jacobson
Joth
J
Zangari
Maurizio
M
Anaissie
Elias
E
Walker
Ron
R
Crowley
John
J
D000686:Amyloidosis / Q000150:complications; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000266:history / Q000627:therapeutic use; D020869:Gene Expression Profiling; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007167:Immunotherapy; D008558:Melphalan / Q000008:administration & dosage / Q000266:history / Q000627:therapeutic use; D009101:Multiple Myeloma / Q000150:complications / Q000235:genetics / Q000266:history / Q000628:therapy*; D036102:Peripheral Blood Stem Cell Transplantation; D011379:Prognosis; D051437:Renal Insufficiency / Q000150:complications; D016879:Salvage Therapy / Q000266:history; D013792:Thalidomide / Q000627:therapeutic use; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
D018906:Antineoplastic Agents, Alkylating; D013792:Thalidomide; D008558:Melphalan