Biologic Correlates of Response and Survival in Patients with Cutaneous T-Cell Lymphoma Treated with Denileukin Diftitox

Denileukin diftitox, a fusion protein consisting of peptide sequences for the enzymatically active and membrane translocation domains of diphtheria toxin and human interleukin, resulted in a response rate of 30% in the phase III registration trial in patients with recurrent or persistent cutaneous T-cell lymphoma (CTCL). Little is known with regard to the biologic correlates of response or the impact of denileukin diftitox on disease progression and survival. In our single-center series of 37 patients with earlyand advanced-stage disease with CTCL treated with denileukin diftitox at a dose of 9 μg/kg or 18 μg/kg per day, we observed an overall response rate of 51%. In 8 patients with early-stage (< IIA) CTCL, there were 5 responses (62.5%), and the median survival has not been reached, with 70% of patients still alive at 46 months. In 29 patients with advanced-stage (≥ IIB) disease, there were 14 responses (49.3%), and the median survival was 31 months. Changes in the number of CD4+CD25+ T-cell populations were observed in 7 of 19 responders, with no overall changes in the absolute lymphocyte counts during the course of therapy. Decrease in lactate dehydrogenase was strongly correlated with clinical response (P < 0.05). Denilekin diftitox was a well-tolerated treatment in early- and advanced-stage CTCL and was not associated with detrimental immunologic efects on lymphocyte populations.