Identifying and Targeting TNF Signaling in Idiopathic Multicentric Castleman’s Disease
Melanie Mumau, Michael V. Gonzalez, Chunyu Ma, Abiola Irvine, Mateo Sarmiento Bustamante, Saishravan Shyamsundar, Luke Y. C. Chen, David Koslicki, David C. Fajgenbaum
Abstract
Idiopathic multicentric Castleman disease (iMCD) is a rare, life-threatening cytokine storm disorder of unknown etiology. 1Patients experience generalized lymphadenopathy, systemic inflammation, and multi-organ failure due to excess interleukin-6 (IL-6) and other cytokines. 2 The most severe form of iMCD involves thrombocytopenia, anasarca, fever, reticulin fibrosis/renal dysfunction, and organomegaly (iMCD-TAFRO).Prognosis is poor; 25-35% of patients die within five years. 3IL-6 inhibition with siltuximab, which is the only FDA-approved therapy for iMCD, is effective in 40-50% of patients, 4 leaving anti-IL-6refractory patients with few therapeutic options.Improved understanding of iMCD-TAFRO pathogenesis is urgently needed to identify new treatments.