RESUMO
BACKGROUND: Sézary syndrome is a leukaemic variant of cutaneous T-cell lymphoma with poor prognosis. With the exception of stem cell transplantation, current treatments for SS are not curative. Rather, they aim at reducing disease burden and improving quality of life. Yet, pruritus - the major cause for impaired quality of life in these patients - is notoriously difficult to treat. Thus, supportive treatments addressing agonizing pruritus are urgently needed. OBJECTIVES: To explore the clinical and immunological effects of type 2 cytokine blockade with dupilumab as supportive treatment in Sézary syndrome. METHODS: A Sézary syndrome patient with stable disease but intractable pruritus was treated with dupilumab in combination with continued extracorporeal photopheresis. Close clinical and immunological monitoring on blood and skin samples from the patient was performed over 44 weeks. In vitro assays with patient's lymphoma cells were performed to address effects of dupilumab on Sézary cell's response to Th2 cytokines. RESULTS: Clinically, dupilumab treatment induced rapid and sustained reduction in itch and improvement of skin and lymph node involvement. In both blood and skin, a reduction in Th2 bias was observed. Intriguingly, lymphocyte counts and Sézary cells in blood increased and later stabilized under dupilumab treatment. In vitro, dupilumab abrogated the anti-apoptotic and activating effects of Th2 cytokines on Sézary cells. CONCLUSIONS: In this Sézary patient, inhibition of IL-4 and IL-13 signalling was associated with striking clinical benefit in terms of quality of life, pruritus and use of topical corticosteroids. While safety remains an important concern, our data support the future exploration of Th2 modulation for supportive care in Sézary Syndrome.
