Bortezomib and Waldenstrom's macroglobulinemia.
Despite advances in therapy, Waldenstrom's macroglobulinemia (WM) remains incurable. Guidelines on therapeutic alternatives in WM recommended the use of alkylating agents, rituximab, nucleoside analogues and anthracyclins either in first line or at relapse and in combination in fit patients. While the overall response rates of combination regimens reached up to 80 - 90% in some studies, the complete response rate is low, no greater than 10 - 20%; and the disease-related median survival for symptomatic patients is approximately 6 years. As such, new therapeutic agents are needed for the treatment of WM. In ongoing efforts, advances were made in the understanding of the biology of WM so as to better target therapeutics for this malignancy. Several preclinical studies have demonstrated that the NFkappaB pathway is a potential target for therapeutics in WM. Bortezomib (Velcade) is the first approved proteasome inhibitor for treating relapse/refractory multiple myeloma and, among other mechanisms of action, significantly inhibits the NFkB pathway. This report provides an update on biological studies and clinical efforts to develop bortezomib as a new treatment of Waldenstrom's macroglobulinemia.
Service des Maladies du Sang, Hopital Huriez, CHRU Lille, Rue Michel Polonovski, Lille, France.
Laurent
L
Pascal
Julie
J
Gay
Christophe
C
Willekens
Mathieu
M
Wemeau
Sandy
S
Balkaran
Daniela
D
Robu
Aldo
A
Roccaro
Pierre
P
Morel
Irene
I
Ghobrial
Xavier
X
Leleu
D000818:Animals; D001897:Boronic Acids / Q000737:chemistry* / Q000627:therapeutic use*; D000069286:Bortezomib; D002986:Clinical Trials as Topic / Q000379:methods / Q000639:trends; D006801:Humans; D011719:Pyrazines / Q000737:chemistry* / Q000627:therapeutic use*; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy* / Q000503:physiopathology
D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib