Cutaneous Lymphoma International Prognostic Index and Risk Stratification in Advanced Mycosis Fungoides and Sézary Syndrome
Abstract
Importance Risk stratification in advanced mycosis fungoides and Sézary syndrome (MF/SS) remains suboptimal given that current TNMB (tumor, node, metastasis, blood) staging has limited prognostic value for clinically relevant outcomes. Objective To determine whether the Cutaneous Lymphoma International Prognostic Index (CLIPI) may be used to predict progression-free survival (PFS) and best objective response (BOR) in patients with advanced MF/SS. Design, Setting, and Participants This international prospective cohort study included patients with stage IIB to IVB MF/SS from the PROCLIPI trial which ran from July 1, 2015, to May 1, 2025, across 46 referral centers. Median follow-up was 4.75 (95% CI, 4.04-5.13) years; eligible participants had complete data on CLIPI, PFS, and BOR. Data were analyzed from September 1 to December 1, 2025. Exposure CLIPI score at diagnosis, based on age (>60 years), elevated serum lactate dehydrogenase, N3 nodal status, and large-cell transformation in the skin. Patients were classified as having low (0 or 1 factor), intermediate (2 factors), or high risk (3 or 4 factors). Main Outcomes and Measures PFS (defined as diagnosis to disease progression or death) and BOR (complete response, partial response, stable disease, or progressive disease) during follow-up. Exploratory analyses evaluated treatment effects before progression using inverse probability weighting. Results Among 277 patients (median [IQR] age at diagnosis, 66 [23-89] years; 183 male individuals [65.7%]), 144 (52.0%) were classified as having low risk, 93 (33.6%) intermediate risk, and 40 (14.4%) high risk. They had a median PFS of 4.64 years (95% CI, 3.50-5.76), 2.72 years (95% CI, 1.81-4.56), and 0.89 years (95% CI, 0.65-1.14), respectively (log-rank P < .001). Patients in the intermediate-risk (hazard ratio [HR], 1.45; 95% CI, 1.01-2.08) and high-risk (HR, 3.84; 95% CI, 2.21-6.66) CLIPI groups displayed higher hazards of progression or death than those at low risk. Inclusion of CLIPI improved PFS discrimination over a model with baseline stage alone. Each 1-point increase in CLIPI was associated with approximately 38% lower odds of observing a better response during follow-up (odds ratio, 0.62; 95% CI, 0.43-0.89). Conclusions and Relevance In this international prospective cohort of patients with advanced MF/SS, CLIPI scores were associated with risk of disease progression and likelihood of response beyond clinical stage. These findings indicate that CLIPI may help to refine risk stratification and support its integration into clinical decision-making and future trial design.
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Authors: Gabriele Roccuzzo, Abraham Bashir, Felicity Evison, Sean Whittaker, Martine Bagot, Emmanuella Guenova, Evangelia Papadavid, Henry Miles Prince, José Antônio Sanches, Denis Miyashiro, Octavio Servitje, Christiane Querfeld, Oleg Akilov, Arvind Arumainathan, Luke Bennett, Maxime Battistella, Mike Bayne, Silvia Alberti Violetti, Paolo Fava, Christoph Iselin, Marie Beylot-Barry, Anne Marie Busschots, Richard Cowan, Reinhard Dummer, Giles Dunnill, Teresa Estrach, Larisa Geskin, Alejandro Ariel Gru, Joan Guitart, Melba Herrera, Emmilia Hodak, Steve Horwitz, Constanze Jonak, Claus‐Detlev Klemke, Robert Knobler, Pam McKay, Márta Marschalkó, Cesare Massone, Rubeta Matin, Christina Mitteldorf, Robert Novoa, Pablo Ortiz‐Romero, Nicola Pimpinelli, Ramon M. Pujol, Kerri E. Rieger, Rudolf Stadler, Franz Trautinger, Johanna Latzka, Maarten Vermeer, Rachel Wachsmuth, Sophie Weatherhead, Ulrike Wehkamp, Marion Wobser, Pietro Quaglino, Youn H. Kim, Julia Scarisbrick
Institutions: University of Pittsburgh, University of Pittsburgh Medical Center, Peter MacCallum Cancer Centre, Northwestern University, King's College - North Carolina, Leiden University Medical Center, Universidade de São Paulo, Universitätsmedizin Göttingen, University of Göttingen, Semmelweis University, Inserm, Universitätsklinikum Würzburg, Northwestern University, Stanford University, Université Paris Cité, Oxford University Hospitals NHS Trust, Stanford Medicine, Université de Bordeaux, University of Zurich, University Hospital Zurich, University of Lausanne, Assistance Publique – Hôpitaux de Paris, University of Florence, Research Institute Hospital 12 de Octubre, Bellvitge University Hospital, Universitat de Barcelona, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Universitair Ziekenhuis Leuven, Johannes Kepler University of Linz, Kepler Universitätsklinikum, Kantonsspital Aarau, Columbia University Irving Medical Center, University of Turin, University Hospitals of the Ruhr-University of Bochum, Hospital Del Mar, University of Southampton, Memorial Sloan Kettering Cancer Center, Medical University of Vienna, National and Kapodistrian University of Athens, City of Hope, Rabin Medical Center, Newcastle upon Tyne Hospitals NHS Foundation Trust, Epworth Hospital, Northwestern Medicine, Ente Ospedaliero Ospedali Galliera, UPMC Hillman Cancer Center, Gloucestershire Hospitals NHS Foundation Trust, City Of Hope National Medical Center, Hôpital Saint-Louis, Bordeaux Population Health, MSH Medical School Hamburg – University of Applied Sciences and Medical University, University Hospital Southampton NHS Foundation Trust, University Hospitals Birmingham NHS Foundation Trust, Royal Devon & Exeter NHS Foundation Trust, Taunton & Somerset NHS Foundation Trust, Beckman Research Institute, Bristol Royal Infirmary, Universitätsklinikum St. Pölten, Clatterbridge Cancer Centre NHS Foundation Trust, Newcastle City Council, Newcastle upon Tyne Hospital, Beatson West of Scotland Cancer Centre, The Christie Hospital, St. Josefskrankenhaus Freiburg, Helios Kliniken