Management of advanced mycosis fungoides and Sézary Syndrome: International Recommendations for systemic treatments and allogeneic hematopoietic cell transplantation from the European Hematology Association, the EORTC Cutaneous Lymphoma Tumours Group
Francesco Onida, Pietro Quaglino, Julia Scarisbrick, Anna Sureda, Emmilia Hodak, Evangelia Papadavid, Silvia Alberti‐Violetti, Martine Bagot, Lorenzo Cerroni, Amrita Goyal‐O'Leary, Rudolf Stadler, Rein Willemze, Jasmine Zain, Marco Ardigò, Emilio Berti, Adèle de Masson, Rafael F. Duarte, Francine Foss, Eva González‐Barca, Joan Guitart, Pablo Ortiz‐Romero, Alessandro Pileri, Pierluigi Porcu, Henry M. Prince, Sima Rozati, Serena Rupoli, Maarten H. Vermeer, Sean Whittaker, Nicola Pimpinelli, Pier Luigi ZinzaniAbstract
Advanced mycosis fungoides (MF) and Sézary syndrome (SS) are the most aggressive forms of cutaneous T‐cell lymphoma and remain associated with a poor prognosis and heterogeneous therapeutic approaches. Recent advances, including targeted therapies and improved transplant strategies, have substantially expanded treatment options, highlighting the need for updated international guidance integrating dermatologic, hematologic, and transplant perspectives. An international multidisciplinary panel convened by the European Hematology Association (EHA), the EORTC Cutaneous Lymphoma Tumours Group (EORTC‐CLTG), the International Society for Cutaneous Lymphoma (ISCL), and the EBMT Lymphoma Working Party reviewed the available evidence and developed consensus recommendations for the management of advanced MF and SS. Thirty international experts participated in the process. Recommendations address diagnostic work‐up, systemic therapies, treatment sequencing, combination strategies, and indications for allogeneic hematopoietic cell transplantation (allo‐HCT). The consensus supports a stage‐adapted and compartment‐oriented therapeutic approach. Immunomodulatory strategies remain central in advanced CTCL: extracorporeal photopheresis is commonly used as first‐line therapy in SS and in patients with significant blood involvement, while interferon‐α and retinoids are widely used in MF, often in combination with skin‐directed therapies. Mogamulizumab and brentuximab vedotin represent key options after prior systemic therapy, with differential activity across skin, blood, and nodal compartments. Combination approaches integrating systemic and skin‐directed treatments may improve response depth and durability. Practical treatment algorithms for advanced MF and SS are proposed to support therapeutic sequencing and multidisciplinary management. Allo‐HCT remains the only potentially curative treatment and should be considered early in selected patients with high‐risk disease features.