Emerging therapies for multiple myeloma.
Multiple myeloma (MM) is a clonal plasma cell malignancy clinically characterized by osteolytic lesions, immunodeficiency, and renal disease. There are an estimated 750,000 people diagnosed with MM worldwide, with a median overall survival of 3 - 5 years. Besides chromosomal aberrations, translocations, and mutations in essential growth and tumor-suppressor genes, accumulating data strongly highlight the pathophysiologic role of the bone marrow (BM) microenvironment in MM pathogenesis. Based on this knowledge, several novel agents have been identified, and treatment options in MM have fundamentally changed during the last decade. Thalidomide, bortezomib, and lenalidomide have been incorporated into conventional cytotoxic and transplantation regimens, first in relapsed and refractory and now also in newly diagnosed MM. Despite these significant advances, there remains an urgent need for more efficacious and tolerable drugs. Indeed, a plethora of preclinical agents awaits translation from the bench to the bedside. This article reviews the scientific rationale of new therapy regimens and newly identified therapeutic agents - small molecules as well as therapeutic antibodies - that hold promise to further improve outcome in MM.
Podar
Klaus
K
Dana-Farber Cancer Institute, Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Boston, MA 02115, USA. klaus_podar@dfci.harvard.edu
Tai
Yu-Tzu
YT
Hideshima
Teru
T
Vallet
Sonia
S
Richardson
Paul G
PG
Anderson
Kenneth C
KC
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001853:Bone Marrow / Q000503:physiopathology*; D002986:Clinical Trials as Topic; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D033581:Stem Cell Transplantation / Q000379:methods; D015996:Survival Rate
D000970:Antineoplastic Agents