OBJECTIVES : Idiopathic multicentric Castleman’s disease (iMCD) is a rare lymphoproliferative disorder associated with considerable patient suffering and potentially life-threatening complications. Current treatments are limited with the international Castleman Disease Collaborative Network (CDCN) guidelines recommending siltuximab, tocilizumab or rituximab. To identify the clinical burden of disease in adults with MCD who are not infected with HIV and HHV-8, a systematic review was conducted.

METHODS : Medline, Embase and the Cochrane library were searched in December 2018. There were no limits on publication language or study inclusion timeframe. Two reviewers screened articles against pre-defined criteria, a third reviewer resolved discrepancies. One analyst extracted data and another quality-controlled it. The DistillerSR Systematic Review Software was used in the studies selection process.

RESULTS : Three clinical trials met inclusion criteria, all using siltuximab. Overall survival (OS) with siltuximab ranged between 100% (year one) and 86-100% (year six). Complete tumour response with siltuximab was between 4-6%, and 25% of siltuximab patients achieved complete symptom response. No placebo-treated patient achieved a complete response. 34% of siltuximab-treated patients and 0% of placebo-treated patients achieved partial durable tumour and symptomatic response. Partial tumour response was reported in 34-48% of siltuximab-treated patients and 0-4% in the placebo arm. For responding subjects, median time to durable tumour and symptomatic response was 155 days vs 65 days (siltuximab vs. placebo, respectively). 38% of patients using placebo discontinued due to adverse events vs. 0-33% of patients on siltuximab. In the three real word evidence studies included, OS varied from 75-100% among tocilizumab-treated patients. 33.3% siltuximab-treated patients with relapsed/refractory iMCD achieved complete response, whereas 25% of tocilizumab-treated patients had complete resolution of symptoms.

CONCLUSIONS : Studies relating to the treatment adults with MCD who are not infected with HIV and HHV-8 are limited. Of the three CDCN recommended treatments, siltuximab’s use is supported by the strongest evidence in iMCD.