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

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.
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.
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.
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.
AuthorsO 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
JournalThe 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
PMID7692295 (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
  • 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

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