LY10 Clinical phenotype and disease burden as determinants of health-related quality of life in mycosis fungoides and Sézary syndrome: insights from the PROCLIPI study

Abstract

Mycosis fungoides (MF) and Sézary syndrome (SS) exhibit marked heterogeneity in cutaneous morphology, disease extent and extracutaneous involvement. While impaired health-related quality of life (HRQoL) is a defining feature of cutaneous T-cell lymphoma (CTCL), the relative contributions of specific dermatological phenotypes and disease characteristics remain incompletely characterized in large, prospective cohorts. Our aim was to identify clinical, morphological and disease-related factors associated with HRQoL impairment in patients with MF and SS enrolled in the international PROCLIPI study. Baseline data from 769 patients with MF or SS enrolled between 2015 and 2024 were analysed. HRQoL was assessed using the Skindex-29 questionnaire. Associations between HRQoL domains (symptoms, emotions, functioning and global score) and demographic, clinical, staging and morphological variables were explored using univariate and multivariate analyses. HRQoL worsened with advancing skin disease burden. Higher modified Severity-Weighted Assessment Tool scores and greater body surface area involvement were strongly associated with worse HRQoL across all domains (P < 0.001). Patients with tumour-stage disease and erythroderma reported the greatest impairment. SS was associated with significantly worse HRQoL than MF, while folliculotropic MF was characterized by increased symptom burden when compared with classic MF. Univariate analyses showed that female sex was associated with poorer HRQoL across all domains, while younger age was associated with poorer emotional HRQoL only. In multivariable analysis, independent predictors of worse HRQoL included erythroderma (β ≈ +1.1), tumour-stage morphology (β ≈ +1.1), alopecia and confluent erythema (all P < 0.001). Male sex and lower age (< 40 years) were independently associated with better HRQoL. This large prospective analysis demonstrates that dermatological phenotype and skin disease burden are key drivers of HRQoL impairment in MF and SS. Routine incorporation of HRQoL assessment may support risk stratification and inform personalized, multidisciplinary supportive care strategies in CTCL.