Radiolabeled-antibody therapy of B-cell lymphoma with autologous bone marrow support.
BACKGROUND
Radiolabeled monoclonal antibodies recognizing B-lymphocyte surface antigens represent a potentially effective new therapy for lymphomas. We assessed the biodistribution, toxicity, and efficacy of anti-CD20 (B1 and 1F5) and anti-CD37 (MB-1) antibodies labeled with iodine-131 in 43 patients with B-cell lymphoma in relapse.


METHODS
Sequential biodistribution studies were performed with escalating doses of antibody (0.5, 2.5, and 10 mg per kilogram of body weight) trace-labeled with 5 to 10 mCi of 131I. The doses of radiation absorbed by tumors and normal organs were estimated by serial gamma-camera imaging and tumor biopsies. Patients whose tumors were estimated to receive greater doses of radiation than the liver, lungs, or kidneys (i.e., patients with a favorable biodistribution) were eligible for therapeutic infusion of 131I-labeled antibodies according to a phase 1 dose-escalation protocol.


RESULTS
Twenty-four patients had a favorable biodistribution, and 19 received therapeutic infusions of 234 to 777 mCi of 131I-labeled antibodies (58 to 1168 mg) followed by autologous marrow reinfusion, resulting in complete remission in 16, a partial response in 2, and a minor response (25 to 50 percent regression of tumor) in 1. Nine patients have remained in continuous complete remission for 3 to 53 months. Toxic effects included myelosuppression, nausea, infections, and two episodes of cardiopulmonary toxicity, and were moderate in patients treated with doses of 131I-labeled antibodies that delivered less than 27.25 Gy to normal organs.


CONCLUSIONS
High-dose radioimmunotherapy with 131I-labeled antibodies is associated with a high response rate in patients with B-cell lymphoma in whom antibody biodistribution is favorable.
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Department of Medicine, University of Washington, Seattle.
Eary
J F
JF
Appelbaum
F R
FR
Martin
P J
PJ
Badger
C C
CC
Nelp
W B
WB
Glenn
S
S
Butchko
G
G
Fisher
D
D
Porter
B
B
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology; D018951:Antigens, CD20; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D000951:Antigens, Neoplasm; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D007457:Iodine Radioisotopes / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000503:physiopathology / Q000532:radiotherapy* / Q000628:therapy*; D008875:Middle Aged; D016499:Radioimmunotherapy; D012074:Remission Induction; D013154:Spleen / Q000503:physiopathology; D059470:Tetraspanins; D014182:Transplantation, Autologous
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018951:Antigens, CD20; D000944:Antigens, Differentiation, B-Lymphocyte; D000951:Antigens, Neoplasm; C059071:CD37 protein, human; D006023:Glycoproteins; D007457:Iodine Radioisotopes; D059470:Tetraspanins