title: Safety of yttrium-90 ibritumomab tiuxetan radioimmunotherapy for relapsed low-grade, follicular, or transformed non-hodgkin's lymphoma.
abstract: OBJECTIVE
  Radioimmunotherapy (RIT) with yttrium-90 ((90)Y)-labeled anti-CD20 antibody ((90)Y ibritumomab tiuxetan; Zevalin, IDEC Pharmaceuticals Corporation, San Diego, CA) has a high rate of tumor response in patients with relapsed or refractory, low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL). This study presents the safety data from 349 patients in five studies of outpatient treatment with (90)Y ibritumomab tiuxetan.
  
  
  METHODS
  Patients received rituximab 250 mg/m(2) on days 1 and 8, and either 0.4 mCi/kg (15 MBq/kg) or 0.3 mCi/kg (11 MBq/kg) of (90)Y ibritumomab tiuxetan on day 8 (maximum dose, 32 mCi). Patients were observed for up to 4 years after therapy or until progressive disease.
  
  
  RESULTS
  Infusion-related toxicities were typically grade 1 or 2 and were associated with rituximab. No significant organ toxicity was noted. Toxicity was primarily hematologic, with nadir counts occurring at 7 to 9 weeks and lasting approximately 1 to 4 weeks depending on the method of calculation. After the 0.4-mCi/kg dose, grade 4 neutropenia, thrombocytopenia, and anemia occurred in 30%, 10%, and 3% of patients, respectively, and after the 0.3-mCi/kg dose, these grade 4 toxicities occurred in 35%, 14%, and 8% of patients, respectively. The risk of hematologic toxicity increased with degree of baseline bone marrow involvement with NHL. Seven percent of patients were hospitalized with infection (3% with neutropenia) and 2% had grade 3 or 4 bleeding events. Myelodysplasia or acute myelogenous leukemia was reported in five patients (1%) 8 to 34 months after treatment.
  
  
  CONCLUSIONS
  Single-dose (90)Y ibritumomab tiuxetan RIT has an acceptable safety profile in relapsed NHL patients with less than 25% lymphoma marrow involvement, adequate marrow reserve, platelets greater than 100,000 cells/ micro L, and neutrophils greater than 1,500 cells/ micro L.
authors.affiliation: Division of Internal Medicine and Hematology and the Department of Radiology, Nuclear Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. witzig@mayo.edu
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
authors.forename: Christine A
authors.initials: CA
authors.lastname: White
authors.forename: Leo I
authors.initials: LI
authors.lastname: Gordon
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Wiseman
authors.forename: Christos
authors.initials: C
authors.lastname: Emmanouilides
authors.forename: James L
authors.initials: JL
authors.lastname: Murray
authors.forename: John
authors.initials: J
authors.lastname: Lister
authors.forename: Pratik S
authors.initials: PS
authors.lastname: Multani
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000633:toxicity; D005260:Female; D006402:Hematologic Diseases / Q000209:etiology; D006801:Humans; D007239:Infections / Q000209:etiology; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000401:mortality / Q000532:radiotherapy*; D008224:Lymphoma, Follicular / Q000276:immunology / Q000401:mortality / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000209:etiology; D016499:Radioimmunotherapy / Q000009:adverse effects; D012449:Safety
chemical_list: D000911:Antibodies, Monoclonal; C422802:ibritumomab tiuxetan