9/13/2023 Data published in Blood Advances supports previously established iMCD treatment Guidelines, with Siltuximab being the most effective first line regimen. Idiopathic multi centric Castleman disease (iMCD) is a rare disease affecting 1000-1200 people annually in the U.S. Treatment guidelines were established in 2018, but their real-world performance has remained unexplored. In a recent study published in Blood Advances, researchers evaluated current treatments for iMCD in the first systematic assessment of the iMCD treatment guidelines. Among 102 iMCD patients, researchers assessed various therapies and their findings support the current treatment guidelines for iMCD, with Siltuximab being the most effective first-line regimen, chemotherapy being effective for severe refractory patients, and to limit the use of corticosteroid mono therapy in the context of iMCD.
Abstract
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 lifethreatening 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{plus minus}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{plus minus}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.