Impact of the number of cycles on efficacy of denileukin diftitox (Dd) in subjects with cutaneous T-cell lymphoma (CTCL)

Abstract

e19549 Background: Dd, a recombinant fusion protein designed to target interleukin-2 receptor-expressing malignancies, is the most extensively studied agent in patients with CTCL. Dd is approved for 8 cycles in CTCL. Here, we present data from study L4389–11 on the effect of treatment course on the efficacy of Dd. Methods: Subjects received Dd doses of 9 or 18 mcg/kg IV daily for 5 days, repeating every 21 days for up to 8 courses. The majority of subjects had CTCL stage ≤ IIa at baseline. Thirty three percent of subjects had received 2 prior anticancer therapies and 23% had received 3 prior anticancer therapies. For all subjects (n=144), the overall median age was 59 years. Tumor burden in skin, blood and lymph nodes and a physician's global assessment were determined at each study visit relative to baseline. Response confirmation was adjudicated by an independent Data Endpoint Review Committee (DERC) after 3 consecutive courses. The primary endpoint was ORR including CR (no clinical evidence of disease based on tumor burden assessments and photography and histopathology of skin biopsy indicated absence of atypical cells), CCR (no clinical evidence of disease based on tumor burden assessments and photography and either the presence of atypical cells was indicated by histopathology of a skin biopsy or histopathology was unavailable) and PR (≥ 50% reduction in measured tumor burden). Data reflect the first treatment course in which the best response was recorded for Dd-treated subjects who responded (n=44) based on the DERC assessment. All responses counted were confirmed in 2 successive assessments. Results: 45% of best responses occurred in cycles 4 thru 8 and the evolution to CR occurred from 4 cycles and beyond. Conclusions: These data support the approved 8 cycles of Dd therapy in CTCL. [Table: see text]