title: Abbreviated chemotherapy with fludarabine followed by tositumomab and iodine I 131 tositumomab for untreated follicular lymphoma.
abstract: OBJECTIVE
  To evaluate the safety and efficacy of a sequential chemotherapy plus radioimmunotherapy (RIT) regimen in previously untreated follicular non-Hodgkin's lymphoma.
  
  
  METHODS
  Thirty-five patients received an abbreviated course (three cycles) of fludarabine followed 6 to 8 weeks later by tositumomab and iodine I 131 tositumomab.
  
  
  RESULTS
  After fludarabine, 31 (89%) of 35 patients responded, with three (9%) of 31 patients achieving a complete response (CR). After the full regimen of fludarabine and iodine I 131 tositumomab, all 35 patients responded; 30 (86%) of 35 patients achieved CR, and five (14%) of 35 achieved partial response. After a median follow-up of 58 months, the median progression-free survival (PFS) had not been reached (95% CI, 27 months to not reached), but it will be at least 48 months. The 5-year estimated PFS rate is 60%. Baseline Follicular Lymphoma International Prognostic Index (FLIPI) was significantly associated (P = .003) with PFS. Five of six patients with more than 25% bone marrow involvement at baseline achieved adequate bone marrow cytoreduction to receive standard-dose iodine I 131 tositumomab. Ten (77%) of 13 patients with baseline bone marrow Bcl-2 positivity demonstrated molecular remissions at month 12. Toxicities were manageable and principally hematologic. Two (6%) of 35 patients developed human antimurine antibodies (HAMA) after RIT.
  
  
  CONCLUSIONS
  Use of abbreviated fludarabine before iodine I 131 tositumomab can reduce bone marrow involvement, when needed, to allow the use of RIT and can suppress HAMA responses. This sequential treatment regimen is highly effective as front-line therapy for follicular lymphoma, particularly for low- or intermediate-risk FLIPI patients.
authors.affiliation: Center for Lymphoma and Myeloma, Division of Hematology and Medical Oncology, Starr Bldg Rm 340, Weill Medical College of Cornell University and New York Presbyterian Hospital, 520 E 70th St, New York, NY 10021, USA. jpleonar@med.cornell.edu
authors.forename: John P
authors.initials: JP
authors.lastname: Leonard
authors.forename: Morton
authors.initials: M
authors.lastname: Coleman
authors.forename: Lale
authors.initials: L
authors.lastname: Kostakoglu
authors.forename: Amy
authors.initials: A
authors.lastname: Chadburn
authors.forename: Ethel
authors.initials: E
authors.lastname: Cesarman
authors.forename: Richard R
authors.initials: RR
authors.lastname: Furman
authors.forename: Michael W
authors.initials: MW
authors.lastname: Schuster
authors.forename: Ruben
authors.initials: R
authors.lastname: Niesvizky
authors.forename: Daniel
authors.initials: D
authors.lastname: Muss
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fiore
authors.forename: Stewart
authors.initials: S
authors.lastname: Kroll
authors.forename: George
authors.initials: G
authors.lastname: Tidmarsh
authors.forename: Shankar
authors.initials: S
authors.lastname: Vallabhajosula
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Goldsmith
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016499:Radioimmunotherapy / Q000379:methods*; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000911:Antibodies, Monoclonal; D014740:Vidarabine; C119496:tositumomab I-131; C024352:fludarabine