Cutaneous T Cell Lymphoma Following Dupilumab Therapy in Patients with Atopic Dermatitis: Clinical Review and Recommendations

Abstract

The complex interplay between atopic dermatitis (AD) and cutaneous T cell lymphomas (CTCL) has been known as a matter of clinical concern. With the widespread use of dupilumab, a monoclonal antibody inhibiting interleukin-4 receptor alpha (IL-4Ra) and interleukin-13 receptor (IL-13R), potential association between dupilumab and developing CTCL has been reported in patients with AD. Disease progression has also been described in patients with known CTCL who were treated with dupilumab. Although population-based and pharmacovigilance data support an increased risk of CTCL with dupilumab use in patients with AD, it is a rare association, most likely occurring in predisposed patients. No evidence is available to support a direct oncogenic risk of transforming AD into lymphoma by the treatment, and current literature suggests the role of IL-4Ra/IL-13R inhibition in unmasking pre-existing malignant T cell clones through increased IL-13 availability. On the basis of a comprehensive literature review and our experience in a cutaneous lymphoma clinic at a tertiary cancer center, we provide practical clinical care recommendations for the use of dupilumab in patients with AD, CTCL, and non-skin lymphomas. We also highlight the need for further researching alternative diagnostic approaches to differentiate CTCL from AD and other inflammatory skin disorders and studying the roles of IL-13 and its receptors in CTCL and the effect of the newly available IL-13-inhibiting therapies.