title: Yttrium-90-labeled anti-CD20 monoclonal antibody therapy of recurrent B-cell lymphoma.
abstract: A Phase I/II dose escalation study of 90Y-murine anti-CD20 monoclonal antibody (mAb) in patients with recurrent B-cell lymphoma was performed. The primary objectives of the study were: (a) to determine the effect of the preinfusion of unlabeled anti-CD20 mAb on the biodistribution of 111In-anti-CD20 mAb; (b) to determine the maximal tolerated dose of 90Y-anti-CD20 mAb that does not require bone marrow transplantation; and (c) to evaluate the safety and antitumor effect of 90Y-anti-CD20 mAb in patients with recurrent B-cell lymphoma. Eighteen patients with relapsed low- or intermediate-grade non-Hodgkin's lymphoma were treated. Biodistribution studies with 111In-anti-CD20 mAb were performed prior to therapy. Groups of three or four patients were treated at dose levels of approximately 13.5, 20, 30, 40, and 50 mCi 90Y-anti-CD20 mAb. Three patients were retreated at the 40-mCi dose level. The use of unlabeled antibody affected the biodistribution favorably. Nonhematological toxicity was minimal. The only significant toxicity was myelosuppression. The overall response rate following a single dose of 90Y-anti-CD20 mAb therapy was 72%, with six complete responses and seven partial responses and freedom from progression of 3-29+ months following treatment. Radioimmunotherapy with </=50 mCi 90Y-anti-CD20 mAb resulted in minimal nonhematological toxicity and durable clinical responses in patients with recurrent B-cell lymphoma. Doses of </=40 mCi 90Y-anti-CD20 mAb were not myeloablative.
authors.affiliation: Departments of Radiation Oncology, Diagnostic Radiology, Division of Nuclear Medicine, Stanford University School of Medicine, Stanford, California, 94305, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Knox
authors.forename: M L
authors.initials: ML
authors.lastname: Goris
authors.forename: K
authors.initials: K
authors.lastname: Trisler
authors.forename: R
authors.initials: R
authors.lastname: Negrin
authors.forename: T
authors.initials: T
authors.lastname: Davis
authors.forename: T M
authors.initials: TM
authors.lastname: Liles
authors.forename: A
authors.initials: A
authors.lastname: Grillo-López
authors.forename: P
authors.initials: P
authors.lastname: Chinn
authors.forename: C
authors.initials: C
authors.lastname: Varns
authors.forename: S C
authors.initials: SC
authors.lastname: Ning
authors.forename: S
authors.initials: S
authors.lastname: Fowler
authors.forename: N
authors.initials: N
authors.lastname: Deb
authors.forename: M
authors.initials: M
authors.lastname: Becker
authors.forename: C
authors.initials: C
authors.lastname: Marquez
authors.forename: R
authors.initials: R
authors.lastname: Levy
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000276:immunology*; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D016499:Radioimmunotherapy / Q000009:adverse effects; D011879:Radiotherapy Dosage; D012008:Recurrence; D014018:Tissue Distribution; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D015021:Yttrium Radioisotopes