Thalidomide and rituximab in Waldenstrom macroglobulinemia.
Thalidomide enhances rituximab-mediated, antibody-dependent, cell-mediated cytotoxicity. We therefore conducted a phase 2 study using thalidomide and rituximab in symptomatic Waldenstrom macroglobulinemia (WM) patients naive to either agent. Intended therapy consisted of daily thalidomide (200 mg for 2 weeks, then 400 mg for 50 weeks) and rituximab (375 mg/m(2) per week) dosed on weeks 2 to 5 and 13 to 16. Twenty-five patients were enrolled, 20 of whom were untreated. Responses were complete response (n = 1), partial response (n = 15), and major response (n = 2), for overall and major response rate of 72% and 64%, respectively, on an intent-to-treat basis. Median serum IgM decreased from 3670 to 1590 mg/dL (P < .001), whereas median hematocrit rose from 33.0% to 37.6% (P = .004) at best response. Median time to progression for responders was 38 months. Peripheral neuropathy to thalidomide was the most common adverse event. Among 11 patients experiencing grade 2 or greater neuropathy, 10 resolved to grade 1 or less at a median of 6.7 months. Thalidomide in combination with rituximab is active and produces long-term responses in WM. Lower doses of thalidomide (ie, <or= 200 mg/day) should be considered given the high frequency of treatment-related neuropathy in this patient population. This trial is registered at www.clinicaltrials.gov as #NCT00142116.
Treon
Steven P
SP
Bing Center for Waldenstrom's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, USA. steven_treon@dfci.harvard.edu
Soumerai
Jacob D
JD
Branagan
Andrew R
AR
Hunter
Zachary R
ZR
Patterson
Christopher J
CJ
Ioakimidis
Leukothea
L
Briccetti
Frederick M
FM
Pasmantier
Mark
M
Zimbler
Harvey
H
Cooper
Robert B
RB
Moore
Maria
M
Hill
John
J
Rauch
Alan
A
Garbo
Lawrence
L
Chu
Luis
L
Chua
Cynthia
C
Nantel
Stephen H
SH
Lovett
David R
DR
Boedeker
Hans
H
Sonneborn
Henry
H
Howard
John
J
Musto
Paul
P
Ciccarelli
Bryan T
BT
Hatjiharissi
Evdoxia
E
Anderson
Kenneth C
KC
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 / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D017452:Receptors, IgG / Q000235:genetics; D000069283:Rituximab; D013792:Thalidomide / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D008258:Waldenstrom Macroglobulinemia / Q000097:blood / Q000188:drug therapy* / Q000235:genetics
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C496124:FCGR3A protein, human; D007075:Immunoglobulin M; D017452:Receptors, IgG; D000069283:Rituximab; D013792:Thalidomide