Treatment of Castleman disease from the perspective of the year 2026

New drugs are continuously entering clinical practice, and therefore opinions on the treatment of Castleman disease are constantly being updated. The text provides information on the treatment of this disease from the perspective of the year 2026.

The treatment of choice for unicentric Castleman disease is surgical removal of the lesion. If its size does not allow for surgery, preoperative pharmacological treatment may be used. There is less experience with radiotherapy in this indication. For multicentric Castleman disease (MCD), it is necessary to rule out possible but rarely detectable etiological causes, infection with human herpesvirus-8 (HHV-8), and association with POEMS syndrome. In HHV-8 positive cases, combinations of rituximab with cytostatics (liposomal doxorubicin, etoposide, or polychemotherapy) are used. In cases of MCD associated with POEMS syndrome, the aim of treatment is to suppress monoclonal gammopathy, which is considered the cause of both MCD and POEMS syndrome. Siltuximab is the treatment of choice for idiopathic multicentric Castleman disease (iMCD). It achieves a therapeutic response in less than 50% of unselected patients. If siltuximab treatment is administered only to patients with markedly elevated inflammatory markers, the number of therapeutic responses is higher. For patients who do not respond adequately to siltuximab, it is necessary to seek second- or third-line treatments. The efficacy of certain drugs in iMCD has been demonstrated not only through case reports but also in clinical studies (rituximab in combination with cytostatics, cyclophosphamide in combination with thalidomide or bortezomib, and sirolimus monotherapy). The efficacy of several other drugs has been shown through case reports or small patient series (anakinra, ruxolitinib, lenalidomide). Given the low incidence of the disease (3-5 per 1 million inhabitants), individual documented cases also provide valid guidance for treatment decisions. This text provides an overview of all experience with the treatment of this disease.

The first-line treatment for iMCD is siltuximab. However, the disease has multiple etiopathogeneses, which is why siltuximab achieved disease symptom resolution in only half of the cases in an unselected population. For second- or third-line treatment, it is necessary to use one of the drugs with proven efficacy in iMCD.