title: Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin's lymphoma.
abstract: OBJECTIVE
  Rituximab is commonly used as a single agent or in combination therapy for non-Hodgkin's lymphoma (NHL). Ibritumomab tiuxetan radioimmunotherapy targets the same antigen as rituximab and has demonstrated efficacy in rituximab-naïve NHL. This study evaluated ibritumomab tiuxetan in the treatment of rituximab-refractory follicular NHL.
  
  
  METHODS
  Eligible patients were refractory to rituximab; this was defined as no objective response to rituximab (375 mg/m(2) weekly for 4 weeks) or time to progression (TTP) of < or = 6 months. The ibritumomab tiuxetan treatment regimen consisted of pretreatment with rituximab (250 mg/m(2) intravenously on days 1 and 8) to deplete peripheral blood B cells, then yttrium-90 ibritumomab tiuxetan (0.4 mCi/kg; maximum, 32 mCi) intravenously on day 8, administered on an outpatient basis. An imaging/dosimetry dose of indium-111 ibritumomab tiuxetan (5 mCi) was injected after rituximab (day 1) in 28 patients.
  
  
  RESULTS
  Fifty-seven patients were treated. The median age was 54 years, 74% had tumors > or = 5 cm, and all were extensively pretreated (median, four prior therapies; range, one to nine). The estimated radiation-absorbed doses to healthy organs were below the study-defined limit in all patients studied with dosimetry. The overall response rate for the 54 patients with follicular NHL was 74% (15% complete responses and 59% partial responses). The Kaplan-Meier-estimated TTP was 6.8 months (range, 1.1 to > or = 25.9 months) for all patients and 8.7 months for responders. Adverse events were primarily hematologic; the incidence of grade 4 neutropenia, thrombocytopenia, and anemia was 35%, 9%, and 4%, respectively.
  
  
  CONCLUSIONS
  Ibritumomab tiuxetan radioimmunotherapy is effective in rituximab-refractory patients. The only significant toxicity is hematologic.
authors.affiliation: Mayo Clinic, 620 Stabile Building, Rochester, MN 55905, USA. witzig@mayo.edu
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
authors.forename: Ian W
authors.initials: IW
authors.lastname: Flinn
authors.forename: Leo I
authors.initials: LI
authors.lastname: Gordon
authors.forename: Christos
authors.initials: C
authors.lastname: Emmanouilides
authors.forename: Myron S
authors.initials: MS
authors.lastname: Czuczman
authors.forename: Mansoor N
authors.initials: MN
authors.lastname: Saleh
authors.forename: Larry
authors.initials: L
authors.lastname: Cripe
authors.forename: Gregory
authors.initials: G
authors.lastname: Wiseman
authors.forename: Teresa
authors.initials: T
authors.lastname: Olejnik
authors.forename: Pratik S
authors.initials: PS
authors.lastname: Multani
authors.forename: Christine A
authors.initials: CA
authors.lastname: White
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008224:Lymphoma, Follicular / Q000628:therapy*; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016499:Radioimmunotherapy / Q000379:methods*; D000069283:Rituximab; D016896:Treatment Outcome; D015021:Yttrium Radioisotopes / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D015021:Yttrium Radioisotopes; D000069283:Rituximab; C422802:ibritumomab tiuxetan