title: Radioimmunotherapy with iodine (131)I tositumomab for relapsed or refractory B-cell non-Hodgkin lymphoma: updated results and long-term follow-up of the University of Michigan experience.
abstract: CD20-targeted radioimmunotherapy is a promising new treatment for B-cell non-Hodgkin lymphoma (NHL). We now provide updated and long-term data on 59 chemotherapy-relapsed/refractory patients treated with iodine (131)I tositumomab in a phase I/II single-center study. Fifty-three patients received individualized therapeutic doses, delivering a specified total-body radiation dose (TBD) based on the clearance rate of a preceding dosimetric dose. Six patients received dosimetric doses only. Dose-escalations of TBD were conducted separately in patients who had or had not undergone a prior autologous stem cell transplant (ASCT) until a nonmyeloablative maximally tolerated TBD was established (non-ASCT = 75 cGy, post-ASCT = 45 cGy). Fourteen additional non-ASCT patients were treated with 75 cGy. Unlabeled antibody was given prior to labeled dosimetric and therapeutic doses to improve biodistribution. Forty-two (71%) of 59 patients responded; 20 (34%) had complete responses (CR). Thirty-five (83%) of 42 with low-grade or transformed NHL responded versus 7 (41%) of 17 with de novo intermediate-grade NHL (P =.005). For all 42 responders, the median progression-free survival was 12 months, 20.3 for those with CR. Seven patients remain in CR 3 to 5.7 years. Sixteen patients were re-treated after progression; 9 responded and 5 had a CR. Reversible hematologic toxicity was dose limiting. Only 10 patients (17%) had human anti-mouse antibodies detected. Long-term, 5 patients developed elevated thyroid-stimulating hormone levels, 5 were diagnosed with myelodysplasia and 3 with solid tumors. A single, well-tolerated treatment with iodine (131)I tositumomab can, therefore, produce frequent and durable responses in NHL, especially low-grade or transformed NHL. (Blood. 2000;96:1259-1266)
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0936, USA. mkaminsk@umich.edu
authors.forename: M S
authors.initials: MS
authors.lastname: Kaminski
authors.forename: J
authors.initials: J
authors.lastname: Estes
authors.forename: K R
authors.initials: KR
authors.lastname: Zasadny
authors.forename: I R
authors.initials: IR
authors.lastname: Francis
authors.forename: C W
authors.initials: CW
authors.lastname: Ross
authors.forename: M
authors.initials: M
authors.lastname: Tuck
authors.forename: D
authors.initials: D
authors.lastname: Regan
authors.forename: S
authors.initials: S
authors.lastname: Fisher
authors.forename: J
authors.initials: J
authors.lastname: Gutierrez
authors.forename: S
authors.initials: S
authors.lastname: Kroll
authors.forename: R
authors.initials: R
authors.lastname: Stagg
authors.forename: G
authors.initials: G
authors.lastname: Tidmarsh
authors.forename: R L
authors.initials: RL
authors.lastname: Wahl
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D018951:Antigens, CD20 / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007457:Iodine Radioisotopes / Q000008:administration & dosage; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D016499:Radioimmunotherapy; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D007457:Iodine Radioisotopes