title: Pivotal study of iodine I 131 tositumomab for chemotherapy-refractory low-grade or transformed low-grade B-cell non-Hodgkin's lymphomas.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of tositumomab and iodine I 131 tositumomab (Bexxar; Corixa Corp, Seattle, WA, and GlaxoSmithKline, Philadelphia, PA) in patients with chemotherapy-refractory low-grade or transformed low-grade non-Hodgkin's lymphoma (NHL) and to compare its efficacy to the patients' last qualifying chemotherapy (LQC) regimens.
  
  
  METHODS
  Sixty patients who had been treated with at least two protocol-specified qualifying chemotherapy regimens and had not responded or progressed within 6 months after their LQC were treated with a single course of iodine I 131 tositumomab.
  
  
  RESULTS
  Patients had received a median of four prior chemotherapy regimens. A partial or complete response (CR) was observed in 39 patients (65%) after iodine I 131 tositumomab, compared with 17 patients (28%) after their LQC (P <.001). The median duration of response (MDR) was 6.5 months after iodine I 131 tositumomab, compared with 3.4 months after the LQC (P <.001). Two patients (3%) had a CR after their LQC, compared with 12 (20%) after iodine I 131 tositumomab (P <.001). The MDR for CR was 6.1 months after the LQC and had not been reached with follow-up of more than 47 months after iodine I 131 tositumomab. An independent review panel verified that 32 (74%) of the 43 patients with nonequivalent durations of response (> 30 days difference) had a longer duration of response after iodine I 131 tositumomab (P <.001). Only one patient was hospitalized for neutropenic fever. Five patients (8%) developed human antimurine antibodies, and one (2%) developed an elevated TSH level after treatment. Myelodysplasia was diagnosed in four patients in follow-up.
  
  
  CONCLUSIONS
  A single course of iodine I 131 tositumomab was significantly more efficacious than the LQC received by extensively pretreated patients with chemotherapy-refractory, low-grade, or transformed low-grade NHL and had an acceptable safety profile.
authors.affiliation: University of Michigan Medical Center, Ann Arbor, MI 48109-0936, USA. mkaminsk@umich.edu
authors.forename: M S
authors.initials: MS
authors.lastname: Kaminski
authors.forename: A D
authors.initials: AD
authors.lastname: Zelenetz
authors.forename: O W
authors.initials: OW
authors.lastname: Press
authors.forename: M
authors.initials: M
authors.lastname: Saleh
authors.forename: J
authors.initials: J
authors.lastname: Leonard
authors.forename: L
authors.initials: L
authors.lastname: Fehrenbacher
authors.forename: T A
authors.initials: TA
authors.lastname: Lister
authors.forename: R J
authors.initials: RJ
authors.lastname: Stagg
authors.forename: G F
authors.initials: GF
authors.lastname: Tidmarsh
authors.forename: S
authors.initials: S
authors.lastname: Kroll
authors.forename: R L
authors.initials: RL
authors.lastname: Wahl
authors.forename: S J
authors.initials: SJ
authors.lastname: Knox
authors.forename: J M
authors.initials: JM
authors.lastname: Vose
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use*; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000532:radiotherapy*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged
chemical_list: D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; C119496:tositumomab I-131