Researchers evaluated an approach to treatment guided by histopathologic subtype in patients with idiopathic multicentric Castleman disease (iMCD), but they found that data were insufficient to support this approach. The results were published in the American Journal of Hematology.

A rare condition, iMCD is marked by features such as systemic inflammation and multicentric lymphadenopathy, according to the researchers. Histopathologic subtypes of iMCD exist, which can be classified as hyaline vascular (also known as hypervascular), plasmacytic, and mixed subtypes. An interleukin-6 (IL-6)-associated pro-inflammatory cytokine storm is thought to often occur with iMCD, which forms the basis for treatment using the anti-IL-6 drug siltuximab. This currently is recommended as a frontline therapy for patients who do not have the hyaline vascular subtype.

The research team sought to determine the appropriateness of using histopathologic subtype to guide siltuximab treatment. They performed secondary analyses of both clinical trial and real-world studies. Clinical trial data involving siltuximab treatment for iMCD included a phase 1 study, a phase 2 study, and a long-term safety study.

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Real-world cases of anti-IL-6 use in patients with iMCD were identified using a PubMed search. This search emphasized severe features with iMCD, specifically the presence of thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO), in patients considered to have hyaline vascular iMCD.

From clinical trial data, the researchers found evidence that clinical benefit with siltuximab occurred in some patients with the hyaline vascular subtype. They also discovered that while the phase 2 study of siltuximab for iMCD suggested poorer responses for patients with the hyaline vascular subtype, independent reviewers only had classified 18 of 79 patients consistently by subtype.

In real-world analyses, anti-IL-6 therapy appeared to show a benefit for patients with hyaline vascular iMCD. In the real-world data, among 18 patients with iMCD-TAFRO and the hyaline vascular histopathology, 14 (78%) showed responses to an anti-IL-6 agent used in a combination therapy. Anti-IL-6 therapy with or without corticosteroids showed a response rate of 69% among 13 patients with hyaline vascular iMCD-TAFRO, although 3 relapses were noted.

The researchers noted that anti-IL-6 therapy may have efficacy in treatment of hyaline vascular iMCD. “Though iMCD histopathology is not supported as a reliable predictor of response to siltuximab at this time, further research is needed to elucidate effective predictive biomarkers,” concluded the researchers.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Fajgenbaum DC, Wu D, Goodman A, et al. Insufficient evidence exists to use histopathologic subtype to guide treatment of idiopathic multicentric Castleman disease. Am J Hematol. Published online September 7, 2020. doi:10.1002/ajh.25992