Novel Therapeutic Strategies for Cutaneous T-Cell Lymphoma in Advanced Stages

The term cutaneous T-cell lymphoma (CTCL), introduced in 1975, was used to describe a spectrum of skin-based malignant tumors of T-cell origin. Immunological studies identified the complex interaction of cytokines released from infiltrating accessory or malignant cells and how such cytokines aid in the maintenance and proliferation of malignant cells. Though the etiology remains unknown, an association with rare retrovirus in some cases has been described. The mainstay of therapy has been to control the cutaneous presentation with topical therapies in patients with early limited-stage disease. However, a significant number of patients develop refractory disease to skin-directed therapies with or without clinical progression to advanced stages requiring systemic therapy. Over the last two decades a wide number of novel agents such as monoclonal antibodies, small molecule inhibitors, and chemotherapy agents have been developed and are used in patients with advanced disease or those who have exhausted topical treatment options and/or radiation. In this contribution we review the results of clinical studies evaluating emerging therapeutic strategies for patients with CTCL that had developed from ongoing translational research programs focused on understanding the biology of different subtypes of CTCL and identifying disease-specific biomarkers suitable for targeting.