Bortezomib in relapsed or refractory Waldenström's macroglobulinemia.
Bortezomib is a proteasome inhibitor that induces apoptosis in primary Waldenström's macroglobulinemia (WM) cells and WM cell lines. To date, 3 clinical trials of single-agent bortezomib in WM have been published. Of the 64 patients pooled from these studies (most with relapsed/refractory disease), a 25% or greater reduction of IgM was achieved in 78%-85%. Responses were rapid in onset, suggesting a role for bortezomib in the management of hyperviscosity or other settings where rapid IgM reduction is indicated. Neuropathy appears more severe and frequent in WM than in myeloma or other indolent lymphomas treated with bortezomib. Bortezomib-based combination therapies, with consideration for attenuated or intermittent dosing of bortezomib to minimize neuropathy, are under investigation.
Princess Margaret Hospital, Toronto, Ontario, Canada. christine.chen@uhn.on.ca
Christine
C
Chen
C Tom
CT
Kouroukis
Darrell
D
White
Michael
M
Voralia
Edward
E
Stadtmauer
A Keith
AK
Stewart
John J
JJ
Wright
Jean
J
Powers
Wendy
W
Walsh
Elizabeth
E
Eisenhauer
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D006801:Humans; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy*
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib