Targeting cutaneous T-cell lymphoma in non-Hodgkin lymphoma: what’s new for investigational agents?

INTRODUCTION: Cutaneous T-cell lymphomas (CTCLs) are a rare group of T-cell lymphomas originating from skin-homing T-lymphocytes. While patients with early-stage disease may have an indolent disease course and excellent survival rates, patients with advanced-stage disease and the aggressive leukemic variant Sézary syndrome (SS) have poor outcomes with poor responses to therapy and short durations of response. New and better treatments are urgently needed for these patients. AREAS COVERED: This review describes the current treatment landscape including underlying disease biology, diagnosis and staging, approaches to therapy with novel FDA-approved agents including brentuximab vedotin, mogamulizumab, and denileukin diftitiox-cdxl. Novel and upcoming biomarkers, drugs, and therapeutic strategies are additionally covered in detail with a focus on safety, efficacy, and compartment-specific effects. EXPERT OPINION: Recent years have seen a shift away from chemotherapy with the approval of targeted therapies like mogamulizumab, brentuximab vedotin, and denileukin diftitox-cxdl. Though these novel agents have improved outcomes for patients with advanced-stage CTCL, most patients will continue to experience relapses. Emerging agents, including lacutamab, resminostat, and immune checkpoint inhibitors and biomarkers including CD5, CD70, and CD47/Sirpα represent the next frontier in maintaining durable remissions and improving quality of life (QoL) for these patients.