Effect of dosing cycles on safety of denileukin diftitox (Dd) in cutaneous T-cell lymphoma (CTCL) patients: Integrated analysis of three phase III studies

Abstract

e19557 Background: Dd is a novel IL-2 receptor-targeted recombinant fusion protein that is approved for treatment of persistent/recurrent CTCL expressing CD25. To date, Dd is the most extensively studied agent in CTCL. The safety of Dd was assessed with respect to dosing cycle in CTCL subjects in 3 large phase III studies: 93–04–10 (study 10), L4389–11 (study 11) and L4389–14 (study 14). Methods: Subjects received Dd doses of 9 or 18 mcg/kg IV daily for 5 days, repeating every 21 days for up to 8 cycles; study 11 also included a placebo arm. Subjects in studies 10 and 11 were CD25(+); study 14 also included CD25(-) subjects. Safety data from these studies were integrated and are presented by dosing cycle. Results: Table 1 shows a summary of all reported adverse events (AEs) by cycle for the 3 studies. For subjects completing at least 4 cycles of Dd treatment the incidence of any AEs was lower in the 3rd and 4th cycles as compared to the 1st and 2nd cycles and the incidence of AEs continued to decrease after cycle 4. Conclusions: In the studies analyzed, the incidence of AEs decreased with each subsequent treatment cycle for subjects receiving Dd. [Table: see text] [Table: see text]