Radiolabeled-Antibody Therapy of B-Cell Lymphoma with Autologous Bone Marrow Support

作者：Oliver W. Press, Janet F. Eary, Frederick R. Appelbaum, Paul J. Martin, Christopher C. Badger, Wil B. Nelp, S. Glenn, Greg Butchko, Darrell R. Fisher, Bruce A. Porter, Dana C. Matthews, Lloyd D. Fisher, Irwin D. Bernstein · 发表于：New England Journal of Medicine · 年份：1993 · DOI：10.1056/nejm199310213291702 · 被引用次数：653 · 研究领域：Radiopharmaceutical Chemistry and Applications、Monoclonal and Polyclonal Antibodies Research、Lymphoma Diagnosis and Treatment

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-la...