Abstract Dupilumab is a monoclonal antibody that binds to interleukin-4 receptor alpha (IL-4Rα) subunit, shared by both IL-4 and IL-13, thereby inhibiting downstream effects of these cytokines. In addition to its role in type 2 (T2) inflammation, IL-4 also contributes to the normal development of adaptive immune responses. We recently demonstrated that chronic IL-4 inhibition leads to decreased post-vaccination responses. Whether it may also contribute to worsening certain hematological malignancies is still under investigation. A relationship or unmasking effect has been demonstrated between dupilumab and worsening of cutaneous T cell lymphomas. To our knowledge, no prior evidence has implicated dupilumab in the development or progression of mantle cell lymphoma. Mantle cell lymphoma derives from mantle zone B cells in the germinal center, and IL-4 is an essential cytokine in germinal center formation. We present the case of a 77-year-old man with history of child-onset asthma who was diagnosed with stage IIIA mantle cell lymphoma (MCL), but did not initially undergo treatment as he was asymptomatic. Eighteen months later, his asthma became uncontrolled despite being on an adequate regimen, so the patient was started on dupilumab, which proved efficacious in improving his asthma symptoms. A year and a half after the initiation of this biologic, the patient’s MCL had nodal progression in the mesenteric, submandibular, paratracheal and subcarinal nodes confirmed by fine needle aspiration, as well as a pleural effusion related to the MCL. The patient received involved field radiation therapy to the submandibular, cervical, and mediastinal areas. Six months after the worsening of his MCL, the patient’s dupilumab was stopped and rituximab was initiated; within three months, his lymphadenopathy improved as demonstrated on a CT chest and abdomen. At this point, the patient’s MCL was declared to be in partial remission. Three months later, however, the patient had worsening shortness of breath, so tezepelumab was initiated. This case demonstrates a temporal association between initiation of dupilumab therapy and the progression of MCL, as well as between cessation of dupilumab and the partial remission of MCL. Although the initiation of treatment with rituximab confounds the clear temporal association between cessation of dupilumab and MCL remission, the observed chronology raises important questions about the safety of dupilumab in patients with certain underlying lymphomas. Specifically, this case highlights the need for systematic evaluation of dupilumab’s potential association with hematologic cancers, including but not limited to cutaneous T cell lymphomas and mantle cell lymphoma. This abstract is funded by: None
Treuth et al. (Fri,) studied this question.