Effect of dose on denileukin diftitox (Dd) response in treatment-naïve cutaneous T-cell lymphoma (CTCL) subjects: A retrospective analysis of three phase III studies

Abstract

e19509 Background: Three phase III studies (10, 11, 14) have been conducted with Dd, a novel IL-2 receptor-targeted recombinant fusion protein, in subjects with CTCL. Dd is approved for the treatment of persistent/recurrent CD25(+) CTCL and is the most extensively studied agent in CTCL. We retrospectively analyzed the efficacy of two Dd doses in treatment-naïve CD25(+) CTCL subjects to understand the relationship between dose and response to therapy. Methods: Studies 10 and 11 included early or advanced stage CD25(+) subjects (CD25 immunostaining in >20% of malignant cells) while 14 included CD25(-). Subjects received 9 or 18 mcg/kg/day IV for 5 days, repeating every 21 days for up to 8 courses; subjects in study 14 only received the higher dose. Study 11 included a placebo arm. Subject demographics were similar among the three studies and between the 2 dose groups in each. Response confirmation required ≥2 consecutive courses (3 observations) and was adjudicated by an independent Data Endpoint Review Committee in each study, using a weighted severity skin, blood and lymph node count. The primary endpoint was ORR (CR, CCR, PR) and the key secondary endpoint was progression-free survival (PFS). Results: Integrated efficacy results for ORR and PFS are shown in the table for treatment-naïve CD25(+) subjects. In general, the nature and incidence of the adverse events reported in the 3 studies were similar, with studies 11 and 14 proving to be broadly consistent with study 10 in terms of safety. Tolerability of 9 and 18 mcg/kg/d was similar in study 10. In study 11, the only AEs that were more frequent in the high-dose group were vomiting (13.3% vs 34.5%) and dysgeusia (0% vs 10.9%). Conclusions: Overall, there was a trend towards higher efficacy favoring 18 mcg/kg/day in treatment-naïve CD25(+) subjects. The ORR was statistically significant for the higher dose group. [Table: see text]