Phase II trial of weekly bortezomib in combination with rituximab in untreated patients with Waldenström Macroglobulinemia.
This study aimed to determine the activity and safety of weekly bortezomib and rituximab in patients with untreated Waldenström Macroglobulinemia (WM). Patients with no prior therapy and symptomatic disease were eligible. Patients received bortezomib IV weekly at 1.6 mg/m(2) on days 1, 8, 15, q 28 days × 6 cycles, and rituximab 375 mg/m(2) weekly on cycles 1 and 4. Primary endpoint was the percent of patients with at least a minor response (MR). Twenty-six patients were treated. At least MR was observed in 23/26 patients (88%) (95% CI: 70-98%) with 1 complete response (4%), 1 near-complete response (4%), 15 partial remission (58%), and 6 MR (23%). Using IgM response evaluated by nephlometry, all 26 patients (100%) achieved at least MR or better. The median time to progression has not been reached, with an estimated 1-year event free rate of 79% (95% CI: 53, 91%). Common grade 3 and 4 therapy related adverse events included reversible neutropenia in 12%, anemia in 8%, and thrombocytopenia in 8%. No grade 3 or 4 neuropathy occurred. The combination of weekly bortezomib and rituximab exhibited significant activity and minimal neurological toxicity in patients with untreated WM.
Ghobrial
Irene M
IM
Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA. irene_ghobrial@dfci.harvard.edu
Xie
Wanling
W
Padmanabhan
Swaminathan
S
Badros
Ashraf
A
Rourke
Meghan
M
Leduc
Renee
R
Chuma
Stacey
S
Kunsman
Janet
J
Warren
Diane
D
Poon
Tiffany
T
Harris
Brianna
B
Sam
Amy
A
Anderson
Kenneth C
KC
Richardson
Paul G
PG
Treon
Steven P
SP
Weller
Edie
E
Matous
Jeffrey
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D000069283:Rituximab; D013997:Time Factors; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy* / Q000401:mortality
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D001897:Boronic Acids; D011719:Pyrazines; D000069283:Rituximab; D000069286:Bortezomib