Yttrium-90-labeled anti-CD20 monoclonal antibody therapy of recurrent B-cell lymphoma.
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.
Knox
S J
SJ
Departments of Radiation Oncology, Diagnostic Radiology, Division of Nuclear Medicine, Stanford University School of Medicine, Stanford, California, 94305, USA.
Goris
M L
ML
Trisler
K
K
Negrin
R
R
Davis
T
T
Liles
T M
TM
Grillo-López
A
A
Chinn
P
P
Varns
C
C
Ning
S C
SC
Fowler
S
S
Deb
N
N
Becker
M
M
Marquez
C
C
Levy
R
R
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*
D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D015021:Yttrium Radioisotopes