title: Fractionated ⁹⁰Y-ibritumomab tiuxetan radioimmunotherapy as an initial therapy of follicular lymphoma: an international phase II study in patients requiring treatment according to GELF/BNLI criteria.
abstract: OBJECTIVE
  We report an international, multicenter phase II trial to evaluate the efficacy and toxicity of fractionated (90)Y-ibritumomab tiuxetan ((90)Y-IT) as initial therapy of follicular lymphoma (FL).
  
  
  METHODS
  A total of 74 patients, with a median age of 61 years (range, 28 to 80 years), were recruited requiring initial therapy by Groupe d'Etude des Lymphomes Folliculaires (GELF)/British National Lymphoma Investigation (BNLI) criteria. Among them, 78% had stage III-IV disease, 32% intermediate, and 44% high-risk (according to FL International Prognostic Index). Treatment consisted of two doses of (90)Y-IT (11.1 MBq/kg) administered 8 to 12 weeks apart. Patients with more than 20% lymphoma infiltration of bone marrow (BM) received one infusion per week for 4 consecutive weeks of rituximab (375 mg/m(2)) and proceeded to fractionated radioimmunotherapy (RIT) only if a repeat BM biopsy demonstrated clearing of lymphoma to less than 20% involvement. The primary end point was end of treatment response of the intention-to-treat population. Secondary objectives were safety and progression-free survival (PFS).
  
  
  RESULTS
  Initial overall response rate (ORR) was 94.4% (68 of 72 patients) with combined complete response (CR/CRu) of 58.3% (42 of 72 patients). Nine patients subsequently improved response making an ORR of 95.8% (69 of 72 patients) and CR/CRu of 69.4% (50 of 72 patients). At a median follow-up of 3.1 years (range, 0.2 to 5.2 years) estimated 3-year PFS is 58%, treatment-free survival 66%, and overall survival 95%. Median PFS is 40.2 months. Thirty patients have experienced disease progression and 24 have required further treatment. The treatment was well tolerated with few (2.8%) grade 3 or 4 infectious episodes or adverse events and manageable hematologic toxicity.
  
  
  CONCLUSIONS
  Fractionated RIT using (90)Y-IT is an effective initial treatment for advanced-stage FL in patients with higher tumor burden requiring treatment.
authors.affiliation: Tim M. Illidge, Sam Mayes, John A. Radford, W. David J. Ryder, Manchester Academic Health Science Centre, University of Manchester; Jill Tipping, Maureen Zivanovic, Christie Hospital NHS Foundation Trust, Manchester; Ruth Pettengell, St. George's, University of London, London; Andrew T. Bates, Southampton University Hospitals NHS Foundation Trust, Southampton; Mike Bayne, Poole Hospital NHS Foundation Trust, Dorset, United Kingdom; Steven Le Gouill, Centre Hospitalier Universitaire Nantes; Françoise Kraeber-Bodere, Caroline Bodet-Milin, University Hospital-ICO-CRCNA INSERM U892, Nantes; Emmanuel Malek, Damien Huglo, Hospitalier Universitaire Lille; Franck Morschhauser, Centre Hospitalier Universitaire, Lille; Fabrice Jardin, Centre Henri Becquerel, Rouen; Manuel Bardies, Centre de Recherche en Cancérologie de Toulouse, Faculté de Médecine de Toulouse-Rangueil, Toulouse, France.
authors.forename: Tim M
authors.initials: TM
authors.lastname: Illidge
authors.forename: Sam
authors.initials: S
authors.lastname: Mayes
authors.forename: Ruth
authors.initials: R
authors.lastname: Pettengell
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Bates
authors.forename: Mike
authors.initials: M
authors.lastname: Bayne
authors.forename: John A
authors.initials: JA
authors.lastname: Radford
authors.forename: W David J
authors.initials: WD
authors.lastname: Ryder
authors.forename: Steven
authors.initials: S
authors.lastname: Le Gouill
authors.forename: Fabrice
authors.initials: F
authors.lastname: Jardin
authors.forename: Jill
authors.initials: J
authors.lastname: Tipping
authors.forename: Maureen
authors.initials: M
authors.lastname: Zivanovic
authors.forename: Françoise
authors.initials: F
authors.lastname: Kraeber-Bodere
authors.forename: Manuel
authors.initials: M
authors.lastname: Bardies
authors.forename: Caroline
authors.initials: C
authors.lastname: Bodet-Milin
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Malek
authors.forename: Damien
authors.initials: D
authors.lastname: Huglo
authors.forename: Franck
authors.initials: F
authors.lastname: Morschhauser
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D007391:International Cooperation; D008224:Lymphoma, Follicular / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D016499:Radioimmunotherapy / Q000379:methods; D012074:Remission Induction; D016896:Treatment Outcome; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D015021:Yttrium Radioisotopes; C422802:ibritumomab tiuxetan