RADIOLABELED ANTmODY THERAPY OF HUMAN B CELL LYMPHOMAS Oliver W. Press. Janet F. Eary. Christopher C. Badger. Paul J. Martin. Frederick R. Appelbaum. Wil B. Nelp. Ron Levy. Richard Miller. Darrell Fisher. Dana Matthews. and Irwin D. Bernstein Departments of Medicine. Nuclear Medicine. and Pediatrics. University of Washington. Seattle. WA 98195. The Fred Hutchinson Cancer Research Center. Seattle. WA 98104. Stanford University. School of Medicine. Stanford. CA 94305. The Battelle Pacific Northwest Laboratories. Richland. WA 99352. and IDEC Pharmaceuticals Corporation. Mountain View. CA 94043
INTRODUCTION
Modern chemotherapy regimens are capable of curing the majority of patients with newly diagnosed diffuse aggressive lymphomas l • but few patients with low-grade lymphomas or relapsed aggressive lymphomas can be cured with conventional therapy. High dose chemoradiotherapy in conjunction with marrow transplantation affords long term disease-free survival for apprOximately 25% of such patients 2 •3 • but toxicity is formidable and post-transplant relapse and treatment-related complications result in the death of most such patients. Targeted radiotherapy using radiolabeled antibodies (RAb) offers a potentially effective new approach for refractory malignancies as demonstrated by a variety of animal and human studies4 - l3 . In this report we summarize our experience administering radiolabeled antiB cell antibodies to patients with refractory non-Hodgkin's lymphomas in a phase I dose escalation trial. EXPERIMENTAL DESIGN AND METHODS Patient Selection: Patients with B cell lymphomas expressing one of the antigens listed in Table I were eligible for this study if they had failed previous conventional therapy. had normal renal and hepatic function. had not received chemotherapy or radiation for four weeks. had no other active medical problems. had an expected survival of at least 60 days. had
INTRODUCTION
Modern chemotherapy regimens are capable of curing the majority of patients with newly diagnosed diffuse aggressive lymphomas l • but few patients with low-grade lymphomas or relapsed aggressive lymphomas can be cured with conventional therapy. High dose chemoradiotherapy in conjunction with marrow transplantation affords long term disease-free survival for apprOximately 25% of such patients 2 •3 • but toxicity is formidable and post-transplant relapse and treatment-related complications result in the death of most such patients. Targeted radiotherapy using radiolabeled antibodies (RAb) offers a potentially effective new approach for refractory malignancies as demonstrated by a variety of animal and human studies4 - l3 . In this report we summarize our experience administering radiolabeled antiB cell antibodies to patients with refractory non-Hodgkin's lymphomas in a phase I dose escalation trial. EXPERIMENTAL DESIGN AND METHODS Patient Selection: Patients with B cell lymphomas expressing one of the antigens listed in Table I were eligible for this study if they had failed previous conventional therapy. had normal renal and hepatic function. had not received chemotherapy or radiation for four weeks. had no other active medical problems. had an expected survival of at least 60 days. had
