Treatment Consistent with Idiopathic Multicentric Castleman Disease Guidelines is Associated with Improved Outcomes

Idiopathic multicentric Castleman disease (iMCD) is a hematologic disorder with an unknown etiology that is diagnosed in approximately 1000-1200 individuals in the US annually. Clinical presentation is heterogeneous, ranging from mild constitutional symptoms with lymphadenopathy to life-threatening multi-organ dysfunction. International, consensus treatment guidelines were developed in 2018. These guidelines relied upon a limited number of clinical trials and small case series; however, real-world performance of these recommendations has not been subsequently studied. Siltuximab, a monoclonal antibody against interleukin 6 (IL6), is approved for the treatment of iMCD and recommended first-line, and tocilizumab, a monoclonal antibody directed against the IL6 receptor, is recommended when siltuximab is unavailable. Chemotherapy, rituximab, and immunomodulators are recommended as second- and third-line treatments based on limited evidence. Corticosteroid monotherapy is used by clinicians, though not recommended. Here, we draw upon the ACCELERATE Natural History Registry to inventory regimens and evaluate regimen response for 102 expert-confirmed iMCD cases. Siltuximab±corticosteroids was associated with a 52% response, while corticosteroid monotherapy was associated with a 3% response. Anti-IL6 directed therapy with siltuximab or tocilizumab demonstrated better response and more durability than was observed with rituximab±corticosteroids. Cytotoxic chemotherapy was associated with a 52% response and was predominantly administered in patients with TAFRO (thrombocytopenia, anasarca, fever, renal failure/reticulin, organomegaly) syndrome. Our results provide evidence in support of current recommendations to administer anti-IL6 first-line, to administer cytotoxic chemotherapy in severe, refractory patients, and to limit corticosteroid monotherapy. These results also demonstrate that evidence remains limited for effective agents for anti-IL6-refractory patients.