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, Richard L. Wahl

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Abstract

Many patients with non-Hodgkin's lymphomas are not cured by current therapies, and new approaches to treatment are needed. As part of an ongoing phase 1 study, we examined the effect of radioimmunotherapy with 131I-labeled B-cell-specific anti-CD20 monoclonal antibody in 10 patients with CD20-positive B-cell lymphomas in whom primary chemotherapy had failed. Anti-B1 (anti-CD20) mouse monoclonal antibody trace-labeled with 131I (15 mg containing 5 mCi) was given intravenously at approximately one-week intervals: first, without pretreatment with unlabeled anti-B1 antibody, to all 10 patients; then with pretreatment with 135 mg of unlabeled antibody, to 8 patients; and then, with pretreatment with 685 mg, to 2 patients. Serial quantitative gamma-camera images and measures of whole-body radioactivity were obtained after each tracer dose. All known disease sites larger than 2 cm could be imaged. The effect of a pretreatment dose of unlabeled anti-B1 antibody on targeting of the tumor with the radiolabeled antibody was variable. The pretreatment dose of unlabeled antibody that produced the highest ratio of the tumor dose to the whole-body dose in tracer studies was then used to deliver higher doses of radioactivity for radioimmunotherapy in nine patients. Three patients received doses designed to deliver 25 cGy to the whole body (two patients treated twice, six to eight weeks apart), four patients received 35 cGy (one patient treated twice), and two patients received 45 cGy (one patient treated twice); each dose contained 34 to 66 mCi of activity. Six of the nine treated patients had tumor responses, including patients with bulky or chemotherapy-resistant disease: four patients had complete remissions, and two had partial responses. Three patients had objective responses to tracer infusions before they received radioimmunotherapeutic doses. Of the four patients with complete remissions, one remained in remission for eight months and the other three continue to have no disease progression (for 11, 9, and 8 months). There was mild or no myelosuppression. Radioimmunotherapy with [131I]anti-B1 antibody is a promising new treatment for lymphoma., Despite the use of various combined chemotherapeutic regimens for advanced-stage intermediate- and high-grade lymphomas, roughly half of patients treated do not have a complete remission or eventually have a relapse after a remission. This situation has not improved noticeably in almost two decades1,2. Treatment with standard-dose salvage chemotherapy rarely results in durable remissions and often has serious toxicity. Although the use of high-dose chemotherapy with bone marrow transplantation has shown promise, not all patients derive long-term benefit from this treatment3. Furthermore, a curative treatment for patients with advanced low-grade lymphoma still remains to be clearly established4

Original languageEnglish
Pages (from-to)459-465
Number of pages7
JournalNew England Journal of Medicine
Volume329
Issue number7
DOIs
StatePublished - Aug 12 1993
Externally publishedYes

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    Kaminski, M. S., Zasadny, K. R., Francis, I. R., Milik, A. W., Ross, C. W., Moon, S. D., Crawford, S. M., Burgess, J. M., Petry, N. A., Butchko, G. M., Glenn, S. D., & Wahl, R. L. (1993). Radioimmunotherapy of B-Cell Lymphoma with [131I]Anti-B1 (Anti-CD20) Antibody. New England Journal of Medicine, 329(7), 459-465. https://doi.org/10.1056/NEJM199308123290703