title: Phase II trial of weekly bortezomib in combination with rituximab in untreated patients with Waldenström Macroglobulinemia.
abstract: 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.
authors.affiliation: Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA. irene_ghobrial@dfci.harvard.edu
authors.forename: Irene M
authors.initials: IM
authors.lastname: Ghobrial
authors.forename: Wanling
authors.initials: W
authors.lastname: Xie
authors.forename: Swaminathan
authors.initials: S
authors.lastname: Padmanabhan
authors.forename: Ashraf
authors.initials: A
authors.lastname: Badros
authors.forename: Meghan
authors.initials: M
authors.lastname: Rourke
authors.forename: Renee
authors.initials: R
authors.lastname: Leduc
authors.forename: Stacey
authors.initials: S
authors.lastname: Chuma
authors.forename: Janet
authors.initials: J
authors.lastname: Kunsman
authors.forename: Diane
authors.initials: D
authors.lastname: Warren
authors.forename: Tiffany
authors.initials: T
authors.lastname: Poon
authors.forename: Brianna
authors.initials: B
authors.lastname: Harris
authors.forename: Amy
authors.initials: A
authors.lastname: Sam
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.forename: Steven P
authors.initials: SP
authors.lastname: Treon
authors.forename: Edie
authors.initials: E
authors.lastname: Weller
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Matous
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D001897:Boronic Acids; D011719:Pyrazines; D000069283:Rituximab; D000069286:Bortezomib