Therapeutic outlook for Castleman’s disease: prospects for the next decade

Abstract

ABSTRACTIntroduction: Castleman disease (CD) is a rare and heterogeneous cluster of disorders, characterized by lymphadenopathy and systemic symptoms. Although most cases of unicentric CD (UCD) are treatable by surgical excision, the prognosis of multicentric CD (MCD) is varied, and it may be challenging to achieve remission. Current treatments of MCD have advanced dramatically with the advent of the novel biologic therapies including interleukin-6 (IL-6) inhibition, but refractory cases occur despite these treatments.Areas covered: We review the etiology and pathogenesis of CD, summarize the current MCD treatments, and discuss the possibilities of a new therapeutic target in severe MCD.Expert opinion: The disease type, the presence of human immunodeficiency virus (HIV) and human herpesvirus 8 (HHV-8), and the progression of organ involvement determines the optimal therapeutic interventions for CD. IL-6 inhibition by tocilizumab or siltuximab has shown effectiveness for HIV/HHV­8-negative patients. Rituximab, alone or in combination with chemotherapy has been used for HIV/HHV-8 negative patients as well as HIV/HHV-8-positive MCD. Antiviral agents are indicated in HIV/HHV-8 positive cases. Novel agents modulating inflammatory pathways such as JAK-STAT signaling and PIK3-Akt-mTOR signaling involved in the pathogenesis of MCD may be candidates for the treatment of severe MCD.