Immune pathways, current and potential therapies in Mycosis fungoides and Sezary syndrome

Primary cutaneous T cell lymphomas (CTCL) comprise a diverse group of malignancies with distinct and variable treatment options and prognoses. Differentiating between subtypes can be challenging due to overlapping heterogeneous clinical and histopathologic features, mandating careful clinicopathologic correlation for diagnosis. Mycosis fungoides (MF) is the most common subtype, whereas the less frequent Sézary syndrome (SS) is viewed at the more aggressive end of the MF/SS spectrum. Large cell transformation (LCT) is a rare phenomenon associated with poor prognosis, arising in a subset of patients with MF/SS, although the exact etiology and molecular pathogenesis remains unclear.

Progression of these diseases is influenced by a variety of immunologic factors. Our advancing understanding of immune pathways and tumor microenvironment may accelerate the development of targeted therapies. This review examines the immune-modulating effects of current and emerging therapeutic drugs for MF/SS. It encompasses both established clinical guidelines and emerging targeted agents currently under investigation in clinical trials.

The treatment landscape for CTCL, especially advanced disease, is becoming increasingly focused on immunotherapies and biologic agents. These treatments have the potential to provide patients with more effective clinical outcomes. The development of synergistic combination therapy will also be important expanding therapeutic options in patients with advanced CTCL.