Multinational prospective cohort study of prognostic value of CLIPI in advanced mycosis fungoides and Sézary syndrome

Risk stratificant in advanced mycosis fungoides and Sézary syndrome (MF/SS) remains suboptimal given that current TNMB staging has limited prognostic value for clinically relevant outcomes. A multinational prospective cohort study using data from the PROCLIPI trial evaluated the prognostic value of the Cutaneous Lymphoma International Prognostic Index (CLIPI) among patients with stage IIB to IVB MF/SS. The study included 277 patients from 46 centers between 2015 and 2025. CLIPI at diagnosis was 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). Outcomes were progression-free survival (PFS) and best objective response (BOR). A total of 144 patients (52.0%) had CLIPI low risk, 93 (33.6%) had intermediate risk, and 40 (14.4%) had high risk. The median PFS in the three groups was 4.64 years, 2.72 years, and 0.89 years (log-rank p<0.001). Patients in the intermediate-risk (HR 1.45; 95% CI 1.01-2.08) and the high-risk (3.84; 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 staging alone. Each 1–point increase in CLIPI was associated with approximately 38% lower odds of observing a better response during follow-up (OR 0.62; 95% CI 0.43-0.89). The authors conclude that in this prospective cohort of patients with advanced MF/SS, CLIPI was associated with risk of disease progression and likelihood of response beyond clinical stage.