Primary therapy of Waldenström macroglobulinemia with bortezomib, dexamethasone, and rituximab: WMCTG clinical trial 05-180.
OBJECTIVE
We examined the activity of bortezomib, dexamethasone, and rituximab (BDR) in patients with symptomatic, untreated Waldenström macroglobulinemia (WM).


METHODS
A cycle of therapy consisted of bortezomib 1.3 mg/m(2) intravenously; dexamethasone 40 mg on days 1, 4, 8, and 11; and rituximab 375 mg/m(2) on day 11. Patients received four consecutive cycles for induction therapy and then four more cycles, each given 3 months apart, for maintenance therapy. Twenty-three patients received a median of seven cycles of treatment.


RESULTS
Median bone marrow disease involvement declined from 55% to 10% (P = .0004), serum immunoglobulin M levels declined from 4,830 to 1,115 mg/dL (P < .0001), and hematocrit increased from 29.8% to 38.2% (P = .0002) at best response. The overall response rates and major response rates were 96% and 83% with three complete responses, two near complete responses, three very good partial responses, 11 partial responses, and three minor responses. Responses occurred at a median of 1.4 months. With a median follow-up of 22.8 months, 18 of 23 patients remained free of disease progression. Peripheral neuropathy was the most common toxicity, and it resolved to grade < or = 1 in 13 of 16 patients at a median of 6.0 months. Four of the first seven treated patients developed herpes zoster, resulting in the institution of prophylactic antiviral therapy.


CONCLUSIONS
The results demonstrate that BDR produces rapid and durable responses, along with high rates of response and complete remissions in WM. Herpes zoster prophylaxis is necessary with BDR, and reversible peripheral neuropathy was the most common toxicity leading to premature discontinuation of bortezomib in 61% of patients. Exploration of alternative schedules for bortezomib administration that includes weekly dosing should be pursued.
Treon
Steven P
SP
Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Harvard Medical School, M547, 44 Binney St, Boston, MA 02115, USA. steven_treon@dfci.harvard.edu
Ioakimidis
Leukothea
L
Soumerai
Jacob D
JD
Patterson
Christopher J
CJ
Sheehy
Patricia
P
Nelson
Marybeth
M
Willen
Michael
M
Matous
Jeffrey
J
Mattern
John
J
Diener
Jakow G
JG
Keogh
George P
GP
Myers
Thomas J
TJ
Boral
Andy
A
Birner
Ann
A
Esseltine
Dixie L
DL
Ghobrial
Irene M
IM
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 / Q000009:adverse effects / Q000627:therapeutic use*; D001809:Blood Viscosity / Q000187:drug effects; D019046:Bone Marrow Neoplasms / Q000188:drug therapy / Q000556:secondary; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006400:Hematocrit; D006562:Herpes Zoster / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D000069283:Rituximab; D016896:Treatment Outcome; D008258:Waldenstrom Macroglobulinemia / Q000097:blood / Q000188:drug therapy* / Q000473:pathology
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D001897:Boronic Acids; D007075:Immunoglobulin M; D011719:Pyrazines; D000069283:Rituximab; D000069286:Bortezomib; D003907:Dexamethasone