Predictive and prognostic biomarkers in patients with Mycosis fungoides and Sézary syndrome (BIO-MUSE): Study protocol for a translational study.

BACKGROUND: Cutaneous T-cell lymphoma (CTCL) is a rare group of lymphomas that primarily affects the skin. Mycosis fungoides (MF) is the most common form of CTCL and Sézary syndrome (SS) is more infrequent. Early stages (IA-IIA) have a favorable prognosis, while advanced stages (IIB-IVB) have a worse prognosis. Around 25% of patients with early stages of disease will progress to advanced stages. Malignant skin-infiltrating T-cells in CTCL are accompanied by infiltrates of non-malignant T-cells and other immune cells that produce cytokines that modulate the inflammation. Skin infection, often with Staphylococcus aureus, is frequent in advanced stages and can lead to sepsis and death. Staphylococcus aureus has also been reported to contribute to progression of disease. Previous reports indicate that a shift from Th1 to Th2 cytokine production and dysfunction of the skin barrier in CTCL. Treatment response is highly variable and often unpredictable, and there is a need for new predictive and prognostic biomarkers.

OBJECTIVE: This prospective translational study aims to identify prognostic biomarkers in the blood and skin of patients with MF and SS.

METHODS: The study aims to recruit 120 adult patients with MF or SS and a control group of 20 healthy volunteers. Treatment will be given according to clinical routine. Sampling of each patient will be performed every three months for three years. Blood samples will be analyzed for lactate dehydrogenase, immunoglobulin E, interleukins, thymus and activation-regulated chemokine (TARC/CCL17) and lymphocyte subpopulations. The lymphoma microenvironment will be investigated through digital spatial profiling and single-cell RNA sequencing. Microbiological sampling and analysis of skin barrier function will be performed. Life quality parameters will be evaluated.

RESULTS: The results will be evaluated in relation to stage of disease. Patient inclusion started in 2021 and is still ongoing in 2023 with 18 patients and 20 healthy controls enrolled. Publication of selected translational findings before the publication of the main results of the trial is accepted.

CONCLUSIONS: The study aims to investigate blood and skin with focus on immune cells and the microbiological environment to identify potential new prognostic biomarkers in MF and SS.

CLINICALTRIAL: Clinicaltrials.gov NCT04904146.