title: Thalidomide and rituximab in Waldenstrom macroglobulinemia.
abstract: 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.
authors: Bing Center for Waldenstrom's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, USA. steven_treon@dfci.harvard.edu
authors: Steven P
authors: SP
authors: Treon
authors: Jacob D
authors: JD
authors: Soumerai
authors: Andrew R
authors: AR
authors: Branagan
authors: Zachary R
authors: ZR
authors: Hunter
authors: Christopher J
authors: CJ
authors: Patterson
authors: Leukothea
authors: L
authors: Ioakimidis
authors: Frederick M
authors: FM
authors: Briccetti
authors: Mark
authors: M
authors: Pasmantier
authors: Harvey
authors: H
authors: Zimbler
authors: Robert B
authors: RB
authors: Cooper
authors: Maria
authors: M
authors: Moore
authors: John
authors: J
authors: Hill
authors: Alan
authors: A
authors: Rauch
authors: Lawrence
authors: L
authors: Garbo
authors: Luis
authors: L
authors: Chu
authors: Cynthia
authors: C
authors: Chua
authors: Stephen H
authors: SH
authors: Nantel
authors: David R
authors: DR
authors: Lovett
authors: Hans
authors: H
authors: Boedeker
authors: Henry
authors: H
authors: Sonneborn
authors: John
authors: J
authors: Howard
authors: Paul
authors: P
authors: Musto
authors: Bryan T
authors: BT
authors: Ciccarelli
authors: Evdoxia
authors: E
authors: Hatjiharissi
authors: Kenneth C
authors: KC
authors: Anderson
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 / 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
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C496124:FCGR3A protein, human; D007075:Immunoglobulin M; D017452:Receptors, IgG; D000069283:Rituximab; D013792:Thalidomide