Existing and Emerging Therapies for Cutaneous T-Cell Lymphoma

Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of non-Hodgkin lymphomas characterized by an infiltration of malignant monoclonal T lymphocytes into the skin. Mycosis fungoides (MF), the most common subtype, and the rarer Sézary syndrome (SS), are considered the classical forms of CTCL, which, because of a varying presentation and lack of genetic and immunophenotypical markers, can often have a delayed diagnosis. With skin-directed topical treatment being the mainstay of therapy in the early stages, there is an absence of long-term curative therapies for advanced disease. Recent insight into the pathogenesis of CTCL has identified new potential therapeutic targets including the monoclonal antibody therapies, brentuximab vedotin and mogamulizumab. Brentuximab vedotin, an anti-CD30 antibody-drug conjugate, received extended approval by the US FDA in 2017 to include primary cutaneous anaplastic large-cell lymphoma and CD30-expressing MF. Mogamulizumab, an anti-CCR4 antibody, received FDA approval in 2018 for relapsed or refractory MF and SS. Further targets and therapies continue to be investigated, including the monoclonal antibody therapy alemtuzumab, an anti-CD52 antibody, and the immune checkpoint blockade therapies, pembrolizumab and nivolumab. These new and emerging targets and therapies may lead to a promising broadening of CTCL treatment options in the future.