RADIOIMMUNOTHERAPY OF B-CELL LYMPHOMA WITH [I-131] ANTI-B1 (ANTI-CD20) ANTIBODY

Background. Many patients with non-Hodgkin's lymphomas are not cured b y current therapies, and new approaches to treatment are needed. As pa rt of an ongoing phase 1 study, we examined the effect of radioimmunot herapy with I-131-labeled B-cell-specific anti-CD20 monoclonal antibod y in 10 patients with CD20-positive B-cell lymphomas in whom primary c hemotherapy had failed. Methods and Results. Anti-B1 (anti-CD20) mouse monoclonal antibody trace-labeled with I-131 (15 mg containing 5 mCi) was given intravenously at approximately one-week intervals: first, w ithout pretreatment with unlabeled anti-B1 antibody, to all 10 patient s; then, with pretreatment with 135 mg of unlabeled antibody, to 8 pat ients; and then, with pretreatment with 685 mg, to 2 patients. Serial quantitative gamma-camera images and measures of whole-body radioactiv ity were obtained after each tracer dose. All known disease sites larg er than 2 cm could be imaged. The effect of a pretreatment dose of unl abeled anti-B1 antibody on targeting of the tumor with the radiolabele d antibody was variable. The pretreatment dose of unlabeled antibody t hat produced the highest ratio of the tumor dose to the whole-body dos e in tracer studies was then used to deliver higher doses of radioacti vity for radioimmunotherapy in nine patients. Three patients received doses designed to deliver 25 cGy to the whole body (two patients treat ed twice, six to eight weeks apart), four patients received 35 cGy (on e patient treated twice), and two patients received 45 cGy (one patien t treated twice); each dose contained 34 to 66 mCi of activity. Six of the nine treated patients had tumor responses, including patients wit h bulky or chemotherapy-resistant disease: four patients had complete remissions, and two had partial responses. Three patients had objectiv e responses to tracer infusions before they received radioimmunotherap eutic doses. Of the four patients with complete remissions, one remain ed 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. Conclusions. Radioimmunotherapy with [I-131]anti-B1 antibody is a promising new treatment for lymphoma.