Novel therapies targeting cutaneous T cell lymphomas and their microenvironment

Cutaneous T-cell lymphomas (CTCL) are rare non-Hodgkin lymphomas with a generally indolent course managed with topical, skin-directed therapies. A small subset, however, will progress to advanced stage disease necessitating systemic therapy for disease control. Currently approved therapies have low response rates and generally short durations of response. Novel therapies, therefore, are urgently needed to address this unmet need. In this review, the mechanisms of CTCL pathogenesis and progression, including the role of the tumor microenvironment and molecular alterations, are summarized. Based on these biologic insights, novel therapies currently under investigation and those with a strong preclinical biologic rationale including T cell and macrophage checkpoint inhibitors, epigenetic regulators, targeted antibodies, tyrosine kinase inhibitors, and apoptosis modulating therapies are discussed.