Denileukin diftitox for the treatment of cutaneous T-cell lymphoma

Introduction: Cutaneous T-cell lymphomas (CTCL) are extranodal non-Hodgkin's lymphomas characterized by the infiltration of malignant T lymphocytes in the skin. The two most common types are mycosis fungoides (MF) and Sezary syndrome (SS). Treatment of MF/SS is complex, and there is a wide array of possible treatment modalities. Unfortunately, no treatment regimens have been proven to prolong survival or cure MF/SS, and therapies are aimed at symptom control and improved quality of life. Areas covered: Denileukin diftitox (DD) is unique among CTCL therapies in that it is a genetically engineered fusion protein that combines the cytotoxic and membrane translocating domains of the diphtheria toxin with a truncated sequence of human IL-2, which binds to high-and intermediate-affinity IL-2 receptors on target cells, is internalized and blocks protein synthesis. This report discusses current treatment options for CTCL and reviews the safety and efficacy data of trials utilizing single-agent DD. Future directions for DD in CTCL are also discussed. Expert opinion: Clinical trials have demonstrated that DD is clearly efficacious in the treatment of CTCL. However, it still remains a therapy utilized beyond the first-line setting of the disease, largely because of the potential toxicities and need for five consecutive daily infusions every 3 weeks. Conversely, there appears to be a subset of patients who achieve very prolonged remissions, sometimes lasting years.