Clinical challenges associated with bortezomib therapy in multiple myeloma and Waldenströms Macroglobulinemia.
Rapid development of the small molecule proteasome inhibitor bortezomib has yielded important clinical benefit for patients with multiple myeloma. Early phase clinical trials suggest the agent has similar efficacy in Waldenströms Macroglobulinemia. Optimization of bortezomib-based therapy, though, requires an understanding of the various challenges associated with use of the drug. This review highlights the rationale for bortezomib therapy in patients with multiple myeloma and Waldenströms Macroglobulinemia, mechanisms of bortezomib resistance, important therapy-related side effects, and new directions for the use of proteasome inhibitors in these disorders.
Laubach
Jacob P
JP
Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA. jacobp_laubach@dfci.harvard.edu
Mitsiades
Constantine S
CS
Roccaro
Aldo M
AM
Ghobrial
Irene M
IM
Anderson
Kenneth C
KC
Richardson
Paul G
PG
D000970:Antineoplastic Agents / Q000627:therapeutic use; D001897:Boronic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy*; D011480:Protease Inhibitors / Q000627:therapeutic use; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy*
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib