Background: Multicentric Castleman’s disease (MCD) is frequently associated with human-herpesvirus (HHV)-8, especially in human immunodeficiency virus (HIV)-1 co-infections. The optimal treatment is unclear. This systematic review provides an overview of available evidence on chemotherapeutic and monoclonal antibody therapies directed against CD20, interleukin (IL)6 or IL6 receptor.
Methods: A systematic literature search of Embase, Medline, Web-of-Science, Scopus, PubMed publisher, Cochrane and Google Scholar was conducted for trials and cohort studies on MCD therapy. Baseline characteristics and reported endpoints were summarised and treatment efficacy was assessed by overall mortality rates.
Results: 1817 studies were identified providing five trials and 14 cohort studies on 666 patients, including one randomised placebo-controlled trial. Ten studies reported on 450 HIV-1 positive patients. Most HIV-1 positive (99.7%), and 24.4% of HIV-1 negative patients were HHV-8 infected. Study populations and methods varied considerably. The use of rituximab was associated with better treatment responses and survival compared with chemotherapy without rituximab in HHV-
associated, predominantly HIV-1 infected, MCD patients. Anti-IL6(receptor) antibodies might be promising second-line or salvage agents, at least in HIV-1 and HHV-8 negative patients. Kaposi sarcoma (re)activation with rituximab and MCD progression to aggressive lymphoma, or haemophagocytic lymphohistiocytosis were important complications.
Conclusions: Optimal MCD treatment for HIV-1 and/or HHV-8 positive or negative patients remains unclear. The available evidence is of low quality due to study designs, treatment allocation bias, and publication bias. MCD patients remain at risk for developing lymphomas or haemophagocytic lymphohistiocytosis. Rituximab may have survival benefits for HHV-8 associated MCD, but it is related to Kaposi sarcoma exacerbations.