Multicenter randomized phase II study of weekly or twice-weekly bortezomib plus rituximab in patients with relapsed or refractory follicular or marginal-zone B-cell lymphoma.
OBJECTIVE
To determine overall response rate (ORR), time to progression (TTP), and duration of response (DOR) with twice-weekly/weekly bortezomib plus rituximab, and evaluate safety/tolerability, in patients with relapsed or refractory CD20(+) follicular lymphoma (FL) or marginal-zone lymphoma.


METHODS
Patients were randomly assigned (minimization method) to bortezomib 1.3 mg/m(2) twice weekly (days 1, 4, 8, and 11; 21-day cycle, five cycles; arm A) or bortezomib 1.6 mg/m(2) weekly (days 1, 8, 15, and 22; 35-day cycle, three cycles; arm B) plus rituximab 375 mg/m(2) weekly for 4 weeks (both arms). Response/progression was determined by International Workshop Response Criteria using oncologist/radiologist-adjudicated data from independent radiology review and investigator assessment.


RESULTS
Eighty-one patients (arm A, n = 41; arm B, n = 40) were enrolled. Dose-intensity was higher in arm A; mean total bortezomib received was similar between arms (18.5 and 17.1 mg/m(2)). In arm A, ORR was 49% (14% complete response [CR]/CR unconfirmed [CRu]), median TTP was 7.0 months, and median DOR was not reached. In arm B, ORR was 43% (10% CR/CRu), and median TTP/DOR were 10.0/9.3 months. The weekly combination regimen seemed better tolerated. Grade 3 or worse adverse events seemed more common in arm A (54%) versus arm B (35%), including thrombocytopenia (10% v 0%) and peripheral neuropathy (10% v 5%), but diarrhea seemed less frequent (7% v 15%). No grade 4 toxicities were reported in arm B.


CONCLUSIONS
Both bortezomib plus rituximab regimens seem feasible in relapsed or refractory indolent lymphomas. The more convenient weekly combination regimen is being compared with single-agent rituximab in an ongoing phase III study in relapsed FL.
de Vos
Sven
S
Division of Hematology/Oncology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA. devos@mednet.ucla.edu
Goy
André
A
Dakhil
Shaker R
SR
Saleh
Mansoor N
MN
McLaughlin
Peter
P
Belt
Robert
R
Flowers
Christopher R
CR
Knapp
Mark
M
Hart
Lowell
L
Patel-Donnelly
Dipti
D
Glenn
Martha
M
Gregory
Stephanie A
SA
Holladay
Charles
C
Zhang
Tracy
T
Boral
Anthony L
AL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000188:drug therapy*; D008224:Lymphoma, Follicular / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000008:administration & dosage; D000069283:Rituximab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D001897:Boronic Acids; D011719:Pyrazines; D000069283:Rituximab; D000069286:Bortezomib