Treating Castleman disease: insights into the use and efficacy of monoclonal antibodies.

INTRODUCTION

Castleman disease (CD) is a rare, heterogeneous group of disorders driven by dysregulated cytokine signaling, particularly interleukin‑6 (IL‑6). Over the past decade, monoclonal antibody (mAb) targeting IL‑6, its receptor, and B‑cell antigens have transformed the management of idiopathic multicentric Castleman disease (iMCD) and related subtypes.

AREAS COVERED: In this review, the authors discuss evidence for mAbs in CD, focusing on siltuximab, tocilizumab, and rituximab, as well as investigational biologics beyond anti-IL-6 and CD20. PubMed/MEDLINE was searched from database inception to May 2026 using terms including 'Castleman disease,' 'siltuximab,' 'tocilizumab,' 'rituximab,' and 'TAFRO,' with emphasis on mAbs in clinical trials, consensus guidelines, real-world cohorts, and mechanistic studies.

EXPERT OPINION: IL-6 blockade remains the foundation of iMCD therapy, and rituximab continues to play a critical role in HHV‑8-associated MCD and iMCD, including idiopathic plasmacytic lymphadenopathy (IPL). However, emerging data increasingly support subtype‑specific and severity‑adapted strategies. Future progress will depend on early identification of IL-6-refractory disease, biomarker-driven treatment selection, and rational combination strategies for aggressive phenotypes such as iMCD-TAFRO.