Phase II trial of weekly bortezomib in combination with rituximab in relapsed or relapsed and refractory Waldenstrom macroglobulinemia.
OBJECTIVE
This study aimed to determine activity and safety of weekly bortezomib and rituximab in patients with relapsed/refractory Waldenström macroglobulinemia (WM).


METHODS
Patients who had at least one previous therapy were eligible. All patients received bortezomib intravenously weekly at 1.6 mg/m(2) on days 1, 8, and 15, every 28 days for six cycles and rituximab 375 mg/m(2) weekly on cycles 1 and 4. The primary end point was the percentage of patients with at least a minor response.


RESULTS
Thirty-seven patients were treated. The majority of patients (78%) completed treatment per protocol. At least minimal response (MR) or better was observed in 81% (95% CI, 65% to 92%), with two patients (5%) in complete remission (CR)/near CR, 17 patients (46%) in partial response, and 11 patients (30%) in MR. The median time to progression was 16.4 months (95% CI, 11.4 to 21.1 months). Death occurred in one patient due to viral pneumonia. The most common grade 3 and 4 therapy-related adverse events included reversible neutropenia in 16%, anemia in 11%, and thrombocytopenia in 14%. Grade 3 peripheral neuropathy occurred in only two patients (5%). The median progression-free (PFS) is 15.6 months (95% CI, 11 to 21 months), with estimated 12-month and 18-month PFS of 57% (95% CI, 39% to 75%) and 45% (95% CI, 27% to 63%), respectively. The median overall survival has not been reached.


CONCLUSIONS
The combination of weekly bortezomib and rituximab showed significant activity and minimal neurologic toxicity in patients with relapsed WM.
Ghobrial
Irene M
IM
Dana-Farber Cancer Institute, Boston, MA 02115, USA. irene_ghobrial@dfci.harvard.edu
Hong
Fangxin
F
Padmanabhan
Swaminathan
S
Badros
Ashraf
A
Rourke
Meghan
M
Leduc
Renee
R
Chuma
Stacey
S
Kunsman
Janet
J
Warren
Diane
D
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 / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000097:blood; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D000069286:Bortezomib; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D012008:Recurrence; D000069283:Rituximab; D016019:Survival Analysis; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy* / Q000276:immunology
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D054316:Biomarkers, Pharmacological; D001897:Boronic Acids; D007075:Immunoglobulin M; D011719:Pyrazines; D000069283:Rituximab; D000069286:Bortezomib