Relapsed/refractory mycosis fungoides and Sezary syndrome: biology, clinical manifestations and therapeutic options

Primary cutaneous T-cell lymphomas (CTCL) are a rare and heterogeneous group, associated with significant morbidity and mortality. Mycosis fungoides (MF), the most common subtype, typically follows an indolent course, whereas Sézary syndrome (SS) is a leukemic and aggressive variant. Treatment strategies for MF are diverse, stage-dependent, and individualized to the patient. While early-stage disease can be effectively managed with skin-directed therapies, advanced or relapsed/refractory disease is associated with a poorer prognosis and frequently necessitates multiple sequential therapies. Current systemic therapeutic options include immunomodulatory drugs, targeted therapies, and chemotherapy, and are aimed at achieving disease control rather than disease cure. Presently, the only potentially curative treatment option is allogeneic stem-cell transplantation. Regional variation in drug access impacts treatment decisions, whilst the evolving landscape of novel agents continues to challenge current paradigms. This review discusses the underlying biology, clinical features, current and emerging therapeutic strategies for relapsed or refractory MF/SS.