Multicenter clinical trial of bortezomib in relapsed/refractory Waldenstrom's macroglobulinemia: results of WMCTG Trial 03-248.
OBJECTIVE
Waldenstrom's macroglobulinemia (WM) is a B-cell disorder. Despite advances in the therapy, WM remains incurable. As such, novel therapeutic agents are needed for the treatment of WM.


METHODS
In this multicenter study, 27 patients with WM received up to eight cycles of bortezomib at 1.3 mg/m(2) on days 1, 4, 8, and 11. All but one patient had relapsed/or refractory disease.


RESULTS
Following therapy, median serum IgM levels declined from 4,660 to 2,092 mg/dL (P < 0.0001). The overall response rate was 85%, with 10 and 13 patients achieving minor and major responses, respectively. Responses were prompt and occurred at median of 1.4 months. The median time to progression for all responding patients was 7.9 (range, 3-21.4+) months. The most common grade III/IV toxicities occurring in > or =5% of patients were sensory neuropathies (22.2%), leukopenia (18.5%), neutropenia (14.8%), dizziness (11.1%), and thrombocytopenia (7.4%). Sensory neuropathies resolved or improved in nearly all patients following cessation of therapy.


CONCLUSIONS
The results of these studies show that bortezomib is an active agent in relapsed and refractory WM.
Treon
Steven P
SP
Bing Center for Waldenstrom's Macroglobulinemia, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. steven_treon@dfci.harvard.edu
Hunter
Zachary R
ZR
Matous
Jeffrey
J
Joyce
Robin M
RM
Mannion
Brian
B
Advani
Ranjana
R
Cook
David
D
Songer
Joseph
J
Hill
John
J
Kaden
Bruce R
BR
Sharon
David
D
Steiss
Ronald
R
Leleu
Xavier
X
Branagan
Andrew R
AR
Badros
Ashraf
A
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000627:therapeutic use*; D012008:Recurrence; D013997:Time Factors; D016896:Treatment Outcome; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy*
D000970:Antineoplastic Agents; D001897:Boronic Acids; D007075:Immunoglobulin M; D011719:Pyrazines; D000069286:Bortezomib