ANTITUMOR-ACTIVITY OF DAB(389)IL-2 FUSION TOXIN IN MYCOSIS-FUNGOIDES

Background: DAB(389)IL-2 is a novel fusion toxin that retargets the cy totoxic A-chain of diphtheria toxin to interleukin-2 (IL-2) receptor-e xpressing tumors. Objective: The purpose of this phase I trial was to study the toxicity, maximum tolerated dose, and clinical efficacy of D AB(389)IL-2 in IL-2 receptor expressing lymphoproliferative malignanci es, including cutaneous T-cell lymphoma. Methods: DAB(389)IL-2 was adm inistered intravenously daily for 5 days every 3 weeks. Dose escalatio n occurred between patient groups. Patients were monitored for laborat ory and clinical toxicity, kinetics, immune response, and clinical eff icacy. Results: Thirty-five patients with cutaneous T-cell lymphoma (i ncluding 30 patients with mycosis fungoides) were treated. Previously, conventional therapy had not worked for 34 of the patients. Thirteen patients (37%) achieved an objective response, including a complete re sponse in five patients (14%). Complete response was achieved in patie nts with extensive erythroderma and tumor stage mycosis fungoides. Adv erse events consisted of reversible fever/chills, hypotension, nausea/ vomiting, and elevation of hepatic transaminase. Doses of less than 31 mu g/kg per day were well tolerated. Clinical responses were observed at all dose levels. Conclusion: DAB(389)IL-2 is well tolerated at dos es of less than 31 mu g/kg per day, and it induced clinical responses in previously treated mycosis fungoides, providing evidence for the an titumor activity of this molecule.