Dupilumab and Systemic Hematologic Malignancies: Case Series and Literature Review

ABSTRACT Background Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting 15%–20% of children and 3%–10% of adults. An increased risk of systemic lymphomas – but not leukemias – has been reported in patients with AD. Dupilumab, a monoclonal IgG4 antibody targeting IL‐4 and IL‐13 signaling, is approved for moderate‐to‐severe AD and is generally well tolerated. Its most common adverse events include injection site reactions, conjunctivitis, upper respiratory tract infections, and headache. However, cutaneous T‐cell lymphomas (CTCL) and other hematologic malignancies have been reported during treatment, though a direct causal link remains unclear. Objectives To describe cases of hematologic malignancies arising during dupilumab treatment for AD and to explore the possible association through a literature review. Methods Four cases of patients with AD who developed hematologic malignancies while on dupilumab therapy were retrospectively identified and analyzed. A literature review was performed to contextualize these findings and assess reported associations between dupilumab and hematologic cancers. Results All four patients developed different forms of hematologic malignancy – including T‐cell and B‐cell lymphomas – after initiating dupilumab. Onset varied from months to years following treatment initiation. The literature review identified additional case reports and series describing similar outcomes, although data remain limited and largely anecdotal. No definitive pathogenic mechanism linking dupilumab to hematologic malignancies has been established. Conclusions Although dupilumab remains a safe and effective treatment for AD, these findings suggest the need for careful monitoring, particularly in patients with risk factors for hematologic disease. Further studies are warranted to clarify whether dupilumab may play a role in unmasking or promoting lymphoproliferative disorders.