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Previous Volume 329:1219-1224 October 21, 1993 Number 17 Next

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ABSTRACT

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.

Source Information

From the Departments of Medicine (O.W.P., F.R.A., P.J.M., C.C.B.), Pediatrics (D.C.M., I.D.B.), Radiology (J.F.E., W.B.N.), Biological Structure (O.W.P.), and Biostatistics (L.D.F.), University of Washington, Seattle; the Fred Hutchinson Cancer Research Center, Seattle (O.W.P., F.R.A., P.J.M., C.C.B., D.C.M., L.D.F., I.D.B.); Coulter Corporation, Miami (S.G., G.B.); First Hill Diagnostic Radiology, Seattle (B.P.); and Battelle Pacific Northwest Laboratories, Richland, Wash. (D.F.).

Address reprint requests to Dr. Press at the University of Washington Cancer Center, Mailstop RC-08, Seattle, WA 98195.

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