Effect of Denileukin Diftitox on Pruritus and Other Skin-Related Symptoms Vs Placebo In Patients with Cutaneous T-Cell Lymphoma

Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of non-Hodgkin's lymphomas (NHLs) that develop primarily in the skin but may progress to involve lymph nodes, blood, and visceral organs. CTCL is characterized by skin patches, plaques, tumors, and erythroderma. Pruritus is frequently associated with skin lesions in CTCL and may be severe. Some treatments have been noted to produce improvements in pruritus that appears to be independent of the response rate. Denileukin diftitox (DD, Ontak), a recombinant fusion protein targeting IL-2-receptor-expressing T lymphocytes, has demonstrated a significant effect on overall response rate with minimal immunosuppression in patients with CD25 assay-positive CTCL. For this post-hoc analysis, we used data from a randomized, double-blind, placebo-controlled, phase III clinical trial to assess the effect of DD on pruritus and overall skin condition in patients with CTCL.

Patients with CD25 assay-positive, stage Ia to III CTCL were randomized to receive 9 μg/kg/d DD (n=45), 18 μg/kg/d DD (n=55), or placebo (n=45). Study medications were administered on the first 5 days of a 21-day cycle for up to 8 cycles. Four grading scales were used to assess clinical signs and symptoms (Table 1).

Higher percentages of DD-treated patients experienced clinically significant improvements in skin-related symptoms than did patients on placebo during treatment and follow-up (Table 2). The differences between the proportions of patients in the placebo group experiencing clinically significant improvement and the proportions of those in the 18 μg/kg/d and combined DD dose groups were statistically significant for all 4 assessments. Substantially more DD-treated patients had ≥20% and ≥50% improvement in pruritus (relative to baseline) at any time than those receiving placebo; improvements were maintained for ≥6 weeks. The global skin score improvement and pruritus score improvement in both high dose and low dose groups were significantly correlated, with higher correlation in high dose group compared to low dose group (p=0.0004 vs p=0.0381). There is no correlation in placebo group for the two scores (p=0.3798). Improvement in pruritis was to some extent independent of response, as demonstrated by the proportion of agreement between tumor response and significant pruritus improvement (27% and 19% for high dose and low dose, respectively, in DD groups), based on Kappa concordance coefficient.

Patients treated with DD, particularly at the 18-μg/kg/d dose, were more likely to experience clinically significant improvements in pruritus and other skin-related symptoms than were patients receiving placebo. DD was observed to improve pruritus independent of response.

Kozlovski: Eisai Inc.: Employment.