PHASE-I TRIAL OF AN INTERLEUKIN-2 FUSION TOXIN (DAB488IL-2) IN HEMATOLOGIC MALIGNANCIES - COMPLETE RESPONSE IN A PATIENT WITH HODGKINS-DISEASE REFRACTORY TO CHEMOTHERAPY

Background. DAB(486)IL-2 is a recombinant fusion toxin in which the na tive diphtheria toxin-receptor binding-domain has been replaced with h uman interleukin-2 (IL-2). This molecule is specifically cytotoxic in vitro within 30 minutes for cells that express the high-affinity IL-2 receptor (IL-BR). Methods. This was a Phase I/II study of DAB(486)IL-8 as a brief infusion in 15 patients with refractory lymphoid malignanc ies. Five patients per cohort received DAB(486)IL-5 as a 30-60 minute intravenous infusion at dose levels of 0.075, 0.115, and 0.2 mg/kg dai ly for 5 days. Results. The maximal tolerated dose (MTD) of DAB(486)IL -2 was determined to be 0.2 mg/kg daily on the basis of hypersensitivi ty-like symptoms and reversible hepatic transaminase elevations. Other adverse effects included mild creatinine elevations, proteinuria, and hypoalbuminemia. The presence of antibodies to diphtheria toxin or DA B(486)IL-2 was correlated with hypersensitivity-like effects but did n ot prevent an antitumor effect. One complete response was observed in a patient with Hodgkin's disease in relapse with bilateral pulmonary n odules after autologous bone marrow transplantation. He remains free o f disease more than 2 years after completion of therapy. Conclusions. The dramatic antitumor response seen in one patient and the relative t olerability of DAB(486)IL-2 indicates the potential utility of this ta rgeted agent in IL-2-expressing hematologic malignancies.