Chimeric Fusion Protein Toxin DAB₄₈₆IL-2 in Advanced Mycosis Fungoides and the Sezary Syndrome: Correlation of Activity and Interleukin-2 Receptor Expression in a Phase II Study

DAB₄₈₆IL-2 is a recombinant toxin with the cell surface-binding domain of diphtheria toxin (DT) replaced by interleukin-2 (IL-2). To correlate clinical response with expression of components of the IL-2 receptor (IL-2R), 14 patients with cutaneous T-cell lymphoma (CTCL) received five daily 90-minute infusions every 21 days. There were no complete responses, 1 partial response (PR), 2 major biologic effects (major cutaneous improvement without change in circulating neoplastic cells), 3 stable disease (SD), and 8 progressive disease (PD). Responders had easily detected expression of CD25 (Tac; α-chain of IL-2R) in skin, and in two responders expression of the β chain of the IL-2 receptor (β-IL-2R) was detectable by reverse transcriptase-polymerase chain reaction. CD25 was also detected in 8 of 11 SD or PD patients, with β-IL-2R in 3 of 8 SD or PD patients. Two of the three responders had anti-DT antibodies before treatment. Reversible increased hepatic transaminases occurred in 13 of 14 patients during the first course, with decreased frequency in repeated courses. The maximal serum concentration after the first infusion of DAB₄₈₆IL-2 varied (1,369 ± 1,155 ng/mL [mean ± SD]; n = 14; range, 55 to 3,999 ng/mL) with a short half-life (T_1/2β = 0.21 ± 0.12 h [mean ± SD]; range, 0.099 to 0.57 h). The area under the concentration curve varied inversely with anti-DT antibody titer. We conclude that DAB₄₈₆IL-2 has valuable activity in certain patients with CTCL. Expression of the IL-2R may be necessary but is not sufficient to predict response. This is a US government work. There are no restrictions on its use.