Emerging trends in the clinical use of bortezomib in multiple myeloma.
Consolidation with high-dose therapy followed by single or double autologous stem cell transplantation has improved response and survival of patients with multiple myeloma (MM), but the disease remains incurable. The emergence of novel agents offer potentially significant advances in the treatment of MM. Bortezomib, a selective inhibitor of the proteasome, has proven to be safe and effective in patients with relapsed and/or refractory MM as monotherapy in phase II/III clinical trials and has produced promising activity in combination regimens with cytotoxic agents. Bortezomib-based combination regimens have also exhibited clinical benefits with manageable toxicities and may ultimately lead to improvement in the duration of response and survival of patients in the first-line setting. High complete and near-complete response rates after 2-4 cycles of bortezomib-based induction therapy may improve outcome in autologous stem cell transplantation recipients. Bortezomib also appears to overcome the adverse prognostic impact of high b2-microglobulin levels and chromosome 13 deletion, as these patients at high risk have shown responses and improved survival with bortezomib therapy. Of interest, patients whose disease previously responded to bortezomib appear to retain sensitivity to the drug, and bortezomib is being explored in maintenance regimens. The use of bortezomib in MM therapy, including ongoing randomized phase III trials, is reviewed herein.
Richardson
Paul G
PG
Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA. paul_richardson@dfci.harvard.edu
Schlossman
Robert
R
Mitsiades
Constantine
C
Hideshima
Teru
T
Munshi
Nikhil
N
Anderson
Kenneth
K
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D004358:Drug Therapy / Q000639:trends; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D033581:Stem Cell Transplantation; D014182:Transplantation, Autologous; D001613:beta 2-Microglobulin / Q000378:metabolism
D000970:Antineoplastic Agents; D001897:Boronic Acids; D061988:Proteasome Inhibitors; D011719:Pyrazines; D001613:beta 2-Microglobulin; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex