Sezary syndrome of cutaneous T-cell lymphoma (CTCL)

Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous and relatively rare family of extranodal non-Hodgkin's lymphomas (NHL) that are primarily localized to the skin. Most patients present with cutaneous patches, plaques, tumors, more rarely with erythroderma. The type of skin lesions and the surface extent of skin involvement, as well as the presence of extracutaneous disease, are the most important prognostic factors in patients with CTCL. Patients with early-stage disease can be effectively treated with skin-directed therapies only. As the disease progresses, systemic therapy often becomes necessary. In this review, we will provide an overview of the systemic treatment options for CTCL, including mechanism of action, efficacy, side effects, and discuss current principles for rational combination therapy and sequential use. Systemic therapy strategies have been evolving with the recent FDA approval of new monoclonal antibodies such as brentuximab vedotin and mogamulizumab to established drugs, such as retinoids, interferons (IFNs), and HDAC inhibitors. Numerous new agents are currently being studied in clinical trials. Identifying the genetic, molecular, and immunologic features of CTCL that are associated with disease progression, drug-resistance, and immune impairment, will optimize the utilization of existing therapies, and facilitate the development of new ones.