Idiopathic multicentric Castleman disease treated with siltuximab for 15 years: a case report
Authors: Lang Evan , Sande Brenda , Brodkin Samantha , van Rhee Frits 
Published: March 2022

Human herpes virus-8 (HHV8)-negative, idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder sustained by pro-inflammatory cytokines, including interleukin-6 (IL-6). According to the international evidence-based criteria developed by the Castleman Disease Collaborative Network (CDCN), siltuximab, which works by inhibiting IL-6, is the recommended choice for iMCD treatment. We report a case of a 63-year-old white male with iMCD who has been on maintenance therapy with siltuximab for 15 years – representing one of the longest treatment periods of any patient with iMCD treated with siltuximab. The patient initially presented with fatigue and night sweats, with progressive worsening of the symptoms. Whole-body positron emission tomography/computed tomography revealed hypermetabolic lymphadenopathy. The patient had histopathologically confirmed Castleman disease, plasma cell type, and was negative for HHV8 and human immunodeficiency virus. The patient had abnormally high C-reactive protein (CRP) levels, a surrogate measure for IL-6. The patient was treated with high-dose steroids but had recurring lymphadenopathy early on. He was enrolled in the phase I dose-finding clinical trial of siltuximab, during which he achieved marked clinical improvement and sustained inhibition of CRP. The patient was enrolled in the long-term safety study and continues to receive siltuximab at 11 mg/kg every 3 weeks. He is presently receiving commercial siltuximab and has remained asymptomatic, with no evidence of lymphadenopathy. The case study presented is consistent with the evidence that siltuximab is a safe and effective therapy for the long-term management of iMCD. In addition, this case highlights the importance of prompt diagnosis for patients with iMCD, as effective therapy is available for patients as described in the CDCN and National Comprehensive Cancer Network iMCD treatment guidelines. Plain Language Summary The case of a 63-year-old white male with idiopathic multicentric Castleman disease who was successfully treated with siltuximab for 15 years Idiopathic multicentric Castleman disease (iMCD) is a group of rare lymphoproliferative disorders with shared histopathological features that affect lymph nodes in multiple regions of the body. The signs and symptoms of iMCD can be varied, with the disease being mild in some patients while life-threatening in others. A timely diagnosis of iMCD can be challenging but is required for effective management. We report a case of a patient who was diagnosed with iMCD. The patient was given high-dose steroids but continued to show progressive disease. He was then started on siltuximab, a targeted antibody therapy against a specific cytokine (interleukin-6) involved in inflammation. The patient responded well to the treatment, has shown evidence of long-term disease control, and has not reported any serious adverse events related to long-term siltuximab use. He has received 11 mg/kg of siltuximab every 3 weeks for the past 15 years. This case emphasizes the value of using siltuximab therapy for long-term management of this rare disorder. In addition, it highlights the importance of prompt diagnosis for patients with iMCD, as effective therapy is available, as described in iMCD treatment guidelines.