Radiolabeled-antibody therapy of B-cell lymphoma with autologous bone marrow support.

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.

• Authors: O W Press, J F Eary, F R Appelbaum, P J Martin, C C Badger, W B Nelp, S Glenn, G Butchko, D Fisher, B Porter
• Journal: The New England journal of medicine (N Engl J Med) Vol. 329 Issue 17 Pg. 1219-24 (Oct 21 1993) ISSN: 0028-4793 [Print] United States
• PMID: 7692295 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Antigens, CD
• Antigens, CD20
• Antigens, Differentiation, B-Lymphocyte
• Antigens, Neoplasm
• CD37 protein, human
• Glycoproteins
• Iodine Radioisotopes
• Tetraspanins

Topics

• Antibodies, Monoclonal
• Antigens, CD (immunology)
• Antigens, CD20
• Antigens, Differentiation, B-Lymphocyte (immunology)
• Antigens, Neoplasm
• Bone Marrow Transplantation
• Combined Modality Therapy
• Glycoproteins (immunology)
• Humans
• Iodine Radioisotopes (administration & dosage, adverse effects, pharmacokinetics)
• Lymphoma, B-Cell (metabolism, physiopathology, radiotherapy, therapy)
• Middle Aged
• Radioimmunotherapy
• Remission Induction
• Spleen (physiopathology)
• Tetraspanins
• Transplantation, Autologous