title: Yttrium 90-ibritumomab tiuxetan plus rituximab maintenance as initial therapy for patients with high-tumor-burden follicular lymphoma: a Wisconsin Oncology Network study.
abstract: BACKGROUND
  Yttrium 90-ibritumomab tiuxetan (90Y-IT) radioimmunotherapy has proved to be effective in relapsed follicular lymphoma (FL). We conducted a clinical trial in which 90Y-IT followed by maintenance rituximab (MR) was evaluated as initial therapy for high-tumor-burden FL.
  
  
  METHODS
  Eligible patients had histologically confirmed FL and met the GELF (Groupe d'Etude des Lymphomes Folliculaires) criteria for high tumor burden. All patients received a single dose of 90Y-IT. Patients with platelet counts of 150,000/mm³ or higher received 0.4 mCi/kg, and patients with platelet counts between 100,000/mm³ and 149,000/mm³ received 0.3 mCi/kg. At 6 months, patients without progressive disease (PD) received rituximab weekly for 4 weeks at a dose of 375 mg/m² (consolidation therapy), followed by MR consisting of the same dose every 3 months for a planned 5 years.
  
  
  RESULTS
  From January 2005 through November 2007, a total of 16 patients were enrolled. The median age was 52 years (range, 37-75). The major toxicity from 90Y-IT was myelosuppression, with 88% and 31% of the patients experiencing grade 3 and grade 4 hematologic toxicity, respectively. The responses to 90Y-IT induction therapy were as follows: 7 patients with complete response/unconfirmed complete response (CR/Cru), 4 with partial response (PR), 3 with stable disease (SD), and 2 with progressive disease (PD). We identified 6 patients with early PD (range, 4-16 months) and 10 patients with prolonged remission (range, 37-101+ months). Compared with the patients who had prolonged remission, the patients who had early PD tended to have larger baseline nodal masses. The median progression-free survival (PFS) has not been reached after a median follow-up period of 48 months. The 3-year PFS and overall survival (OS) rates were 56% (95% CI, 37%-87%) and 93% (95% CI, 80%-100%), respectively.
  
  
  CONCLUSIONS
  The overall response rate (ORR) to 90Y-IT was 69% in patients who had previously untreated, high-tumor-burden FL, which is lower than what is observed with contemporary rituximab/chemotherapy combinations. MR after 90Y-IT did convert all PRs to CRs. Alternative therapies should be considered for patients who have FL with large nodal masses (>9 cm), whereas very durable responses are possible in patients who have intermediate-size masses (>9 cm).
authors.affiliation: University of Wisconsin, Madison, Wisconsin.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Rajguru
authors.affiliation: Reykjavik, Iceland.
authors.forename: Thorhildur
authors.initials: T
authors.lastname: Kristinsdottir
authors.affiliation: University of Wisconsin, Madison, Wisconsin.
authors.forename: Jens
authors.initials: J
authors.lastname: Eickhoff
authors.affiliation: Aspirus Hospital, Wausau, Wisconsin.
authors.forename: Chris
authors.initials: C
authors.lastname: Peterson
authors.affiliation: Gundersen Health System, LaCrosse, Wisconsin.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Meyer
authors.affiliation: University of Wisconsin and UW Carbone Cancer Center, Madison, Wisconsin.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Traynor
authors.affiliation: University of Wisconsin and UW Carbone Cancer Center, Madison, Wisconsin.
authors.forename: Brad S
authors.initials: BS
authors.lastname: Kahl
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008224:Lymphoma, Follicular / Q000175:diagnosis / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D016499:Radioimmunotherapy; D000069283:Rituximab; D016896:Treatment Outcome; D047368:Tumor Burden; D014922:Wisconsin; D015021:Yttrium Radioisotopes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D015021:Yttrium Radioisotopes; D000069283:Rituximab; C422802:ibritumomab tiuxetan