There are two types of cutaneous T-cell lymphoma, or CTCL, which fall under the non-Hodgkin’s Lymphoma umbrella; Mycosis Fungoides (MF) presents with skin patches or tumorous plaques and Sezary Syndrome (SS) presents with a thin itchy rash and must also involve lymphoma cells in the bloodstream. CTCL is one of the most common types of T-cell lymphoma. Current treatment options include both topical and systemic therapies depending on the extent of disease at the time of diagnosis. While many patients can complete traditional treatment and live healthy lives, there are a subset of patients with relapsed or refractory disease which becomes harder to treat. This group of patients have not had many options until now. The FDA has just recently approved a new drug called mogamulizumab-kpkc (Poteligeo, Kyowa Hakko Kirin Pharma), which is specific for MF and SS which are harder to treat types of non-Hodgkin’s lymphoma.
Mogamulizumab-kpkc is a directed monoclonal antibody that binds to a specific chemokine receptor, CCR4. This receptor expression is found on cells involved in our innate and adaptive immune systems and has been documented as a present marker in CTCL. A large phase III clinical trial (NCT01728805) compared this drug mogamulizumab-kpkc, named KW-0761, with the current vorinostat (Zolinza, Merck) therapy for CTCL. The study involved 372 participants across the United States, Australia, multiple countries in Europe, and Japan. Progression free survival was significant for those participants receiving KW-0761. While there were some adverse reactions reported, the drug is a breakthrough and Cfills a needed gap for patients with these types of T-cell lymphomas.
Mogamulizumab acts by reducing the number of CCR4-expressing cells through the well described process of antibody dependent, cell-mediated cytotoxicity. This is an immune system response using Fc receptor effector cells which recognize and destroy targeted cells identified by the specific antibodies covering their pathogenic antigens. In this case, the pathogenic antigen is CCR4. The antibody dependent, cell-mediated cytotoxicity pathway utilizes cytotoxic granule release and is already used in the body for protection against infectious diseases. The model for monoclonal antibody use in cancer therapy has been proven effective over the past few years of research and clinical application.