Radioimmunotherapy of B-Cell Lymphoma with [131I]Anti-B1 (Anti-CD20) Antibody
Mark S. Kaminski, Kenneth R. Zasadny, Isaac R. Francis, Adam W. Milik, Charles W. Ross, Scott D. Moon, Shelley M. Crawford, Jeanne M. Burgess, Neil A. Petry, Gregory M. Butchko, Stephan D. Glenn, and Richard L. Wahl
Background Many patients with non-Hodgkin's lymphomas are notcured by current therapies, and new approaches to treatmentare needed. As part of an ongoing phase 1 study, we examinedthe effect of radioimmunotherapy with 131I-labeled B-cell-specificanti-CD20 monoclonal antibody in 10 patients with CD20-positiveB-cell lymphomas in whom primary chemotherapy had failed.
Methods and Results Anti-B1 (anti-CD20) mouse monoclonal antibodytrace-labeled with 131I (15 mg containing 5 mCi) was given intravenouslyat approximately one-week intervals: first, without pretreatmentwith unlabeled anti-B1 antibody, to all 10 patients; then withpretreatment with 135 mg of unlabeled antibody, to 8 patients;and then, with pretreatment with 685 mg, to 2 patients. Serialquantitative gamma-camera images and measures of whole-bodyradioactivity were obtained after each tracer dose. All knowndisease sites larger than 2 cm could be imaged. The effect ofa pretreatment dose of unlabeled anti-B1 antibody on targetingof the tumor with the radiolabeled antibody was variable.
The pretreatment dose of unlabeled antibody that produced thehighest ratio of the tumor dose to the whole-body dose in tracerstudies was then used to deliver higher doses of radioactivityfor radioimmunotherapy in nine patients. Three patients receiveddoses designed to deliver 25 cGy to the whole body (two patientstreated twice, six to eight weeks apart), four patients received35 cGy (one patient treated twice), and two patients received45 cGy (one patient treated twice); each dose contained 34 to66 mCi of activity. Six of the nine treated patients had tumorresponses, including patients with bulky or chemotherapy-resistantdisease: four patients had complete remissions, and two hadpartial responses. Three patients had objective responses totracer infusions before they received radioimmunotherapeuticdoses. Of the four patients with complete remissions, one remainedin remission for eight months and the other three continue tohave no disease progression (for 11, 9, and 8 months). Therewas mild or no myelosuppression.
Conclusions Radioimmunotherapy with [131I]anti-B1 antibody isa promising new treatment for lymphoma.
Source Information
From the Divisions of Hematology/Oncology (M.S.K., A.W.M., J.M.B.) and Nuclear Medicine (K.R.Z., S.D.M., S.M.C., N.A.P., R.L.W.), Department of Internal Medicine, and the Departments of Radiology (I.R.F., R.L.W.) and Pathology (C.W.R.), University of Michigan, Ann Arbor; and the Coulter Corporation (G.M.B., S.D.G.), Hialeah, Fla.
Address reprint requests to Dr. Kaminski at the Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Medical Center, 102 Observatory St., Ann Arbor, MI 48109-0724.
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