EORTC Consensus Recommendations for MF and Sézary Syndrome Treatment (PDF)

European Journal of Cancer 195 (2023) 113343 Contents lists available at ScienceDirect European Journa...

European Journal of Cancer 195 (2023) 113343 Contents lists available at ScienceDirect European Journal of Cancer journal homepage: www.ejcancer.com Review EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome – Update 2023 Johanna Latzka a, b, *, Chalid Assaf c, d, e, Martine Bagot f, Antonio Cozzio g, Reinhard Dummer h, Emmanuella Guenova i, Robert Gniadecki j, k, Emmilia Hodak l, Constanze Jonak m, Claus-Detlev Klemke n, Robert Knobler m, Stephen Morrris o, Jan P. Nicolay p, Pablo L. Ortiz-Romero q, Evangelia Papadavid r, Nicola Pimpinelli s, Pietro Quaglino t, Annamari Ranki u, Julia Scarisbrick v, Rudolf Stadler w, Liisa Väkevä u, Maarten H. Vermeer x, Ulrike Wehkamp y, z, Sean Whittaker aa, Rein Willemze x, Franz Trautinger a, b a Department of Dermatology and Venereology, University Hospital of St. Pölten, Karl Landsteiner University of Health Sciences, St. Pölten, Austria b Karl Landsteiner Institute of Dermatological Research, Department of Dermatology and Venereology, University Hospital of St. Pölten, St. Pölten, Austria c Department of Dermatology, HELIOS Klinikum Krefeld, Krefeld, Germany d Institute for Molecular Medicine, Medical School Hamburg, University of Applied Sciences and Medical University, Hamburg, Germany e Department of Dermatology, HELIOS Klinikum Schwerin, University Campus of The Medical School Hamburg, Schwerin, Germany f Department of Dermatology, Hopital Saint Louis, Université Paris Cité, INSERM U976, Paris, France g Department of Dermatology and Allergology, Kantonspital St. Gallen, St. Gallen, Switzerland h Department of Dermatology, University of Zurich, Zurich, Switzerland i Department of Dermatology, University Hospital of Lausanne and Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland j Department of Dermatology, University of Copenhagen, Copenhagen, Denmark k Division of Dermatology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada l Cutaneous Lymphoma Unit, Davidoff Cancer Center, Rabin Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel m Department of Dermatology, Medical University of Vienna, Vienna, Austria n Hautklinik, Städtisches Klinikum Karlsruhe, Karlsruhe, Germany o Guy’s and St Thomas’ NHS Foundation Trust, Guy’s Hospital, London, UK p Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Mannheim, Germany q Department of Dermatology, Hospital Universitario 12 de Octubre, Institute i+12, CIBERONC, Medical School, University Complutense, Madrid, Spain r National and Kapodistrian University of Athens, 2nd Department of Dermatology and Venereology, Attikon General Hospital, University of Athens, Chaidari, Greece s Department of Health Sciences, Division of Dermatology, University of Florence, Florence, Italy t Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy u Department of Dermatology and Allergology, Inflammation Center, Helsinki University Central Hospital, Helsinki, Finland v Department of Dermatology, University Hospital Birmingham, Birmingham, UK w University Department of Dermatology, Venereology, Allergology and Phlebology, Skin Cancer Center, Johannes Wesling Medical Centre Minden, Ruhr University Bochum, Bochum, Germany x Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands y Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany z Medical Department, Medical School of Hamburg, Hamburg, Germany aa St. John’s Institute of Dermatology, School of Basic and Medical Biosciences, Faculty of Life Sciences and Medicine, King’s College London, London, UK A R T I C L E I N F O A B S T R A C T Keywords: On behalf of the EORTC Cutaneous Lymphoma Tumours Group (EORTC-CLTG) and following up on earlier Mycosis fungoides versions published in 2006 and 2017 this document provides an updated standard for the treatment of mycosis Sézary syndrome fungoides and Sézary syndrome (MF/SS). It considers recent relevant publications and treatment options Cutaneous T-cell lymphomas introduced into clinical practice after 2017. Total skin electron beam therapy Consensus was established among the authors through a series of consecutive consultations in writing and a Radiotherapy round of discussion. Treatment options are assigned to each disease stage and, whenever possible and clinically Phototherapy useful, separated into first- and second line options annotated with levels of evidence. Chemotherapy * Corresponding author: Department of Dermatology and Venereology, University Hospital of St. Pölten, Dunant-Platz 1, A-3100 St. Pölten, Austria. E-mail address: [email protected] (J. Latzka). https://doi.org/10.1016/j.ejca.2023.113343 Received 5 May 2023; Received in revised form 28 July 2023; Accepted 23 August 2023 Available online 18 September 2023 0959-8049/© 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by- nc-nd/4.0/). J. Latzka et al. European Journal of Cancer 195 (2023) 113343 Immunotherapy Major changes to the previous version include the incorporation of chlormethine, brentuximab vedotin, and Retinoids Corticosteroids mogamulizumab, recommendations on the use of pegylated interferon α (after withdrawal of recombinant unpegylated interferons), and the addition of paragraphs on supportive therapy and on the care of older patients. Still, skin-directed therapies are the most appropriate option for early-stage MF and most patients have a normal life expectancy but may suffer morbidity and impaired quality of life. In advanced disease treatment options have expanded recently. Most patients receive multiple consecutive therapies with treatments often having a relatively short duration of response. For those patients prognosis is still poor and only for a highly selected subset long term remission can be achieved with allogeneic stem cell transplantation. Understanding of the disease, its epidemiology and clinical course, and its most appropriate management are gradually advancing, and there is well-founded hope that this will lead to further improvements in the care of patients with MF/SS. 1. Introduction current Tumor (skin) Lymph nodes Metastasis (viscera) Blood (TNMB)- staging classification is provided in Tables 2 and 3. For a detailed In 2004 the European Organisation of Research and Treatment of description of the clinical and pathological characteristics of MF and its Cancer (EORTC) Cutaneous Lymphoma Task Force (now Cutaneous variants and of SS see earlier published reviews [2,8,9]. Lymphoma Tumour Group) organised a workshop to initiate the Finally, before going into detail of therapeutic options and before development and publication of a European consensus on the treatment considering who should be treated how, it is still and of unchanged of mycosis fungoides (MF) and Sézary Syndrome (SS). This effort importance to keep in mind that, although appropriate treatment will be resulted in the publication of the first EORTC-consensus recommenda­ effective in most patients, therapy in MF/SS is generally palliative and tions for the treatment of MF/SS in 2006 to be revised and updated in should follow a step wise, stage-adapted approach giving priority to 2017. Since then, the disease classification has again been refined, maintenance of quality of life. Remarkable exceptions to this existing treatment regimens modified or removed and novel modalities principle are allogeneic stem cell transplantation (alloSCT) in advanced introduced, necessitating another update, which is presented here [1–3]. disease and the anecdotal patient with long term remission after Maintaining its original structure (stage-wise recommendations, skin-directed therapy (SDT) in localised early stages, where the primary separated into first- and second line options, wherever appropriate), intention of treatment is curative. reference to the previous version of the recommendations will be made In an orphan condition and with evidence from larger randomised whenever possible to avoid redundancy and duplication. At the same controlled trials still rare, guidelines developed by various national and time some parts of the previous version will again be included to international groups help with decision making [11–15]. The treatment maintain readability and the use as an aid to clinical decision making. recommendations provided here represent an updated consensus Current definition of cutaneous T-cell lymphomas (CTCL), a group of rare non-Hodgkin lymphomas, follows the 5th edition of the WHO classification of haematolymphoid tumours, that largely incorporates Table 2 the WHO-EORTC classification for cutaneous lymphomas published in TNMB staging for mycosis fungoides and Sézary syndrome. 2019 (Table 1) [2,4]. Since MF (including its variants) is the most Skin common entity among CTCL and since it shares many features with the T1 Limited patches, papules, and/or plaques covering 5% of peripheral blood lymphocytes are Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T- 9709/3 atypical (Sézary) cells but does not meet the criteria of B2 cell lymphoma B1a Clone negative Primary cutaneous γ/δ T-cell lymphoma 9726/3 B1b Clone positive Primary cutaneous CD4+ small/medium T-cell lymphoproliferative 9709/1 B2 High blood tumour burden: ≥1000/μl Sézary cells with positive clone disorder SS is staged as T4 N2/3/x M0 B2. Primary cutaneous acral CD8+ T-cell lymphoproliferative disorder* 9709/3 * Blood staging for MF/SS is further defined as B0 =