Siltuximab, a novel anti-interleukin-6 monoclonal antibody, for Castleman's disease

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Frits van RheeRazelle Kurzrock

Abstract

Interleukin-6 (IL-6) has emerged as a key factor in the pathogenesis of the atypical lymphoproliferative disorder Castleman's disease (CD). Siltuximab is a new anti-IL-6, chimeric monoclonal antibody with potential therapeutic benefit in patients with CD. We report interim results from an open-label, dose-finding, seven-cohort, phase I study in which patients with symptomatic, multicentric or unresectable, unicentric CD received siltuximab at 1-, 2-, or 3-week intervals. The main efficacy end point of clinical benefit response (CBR) was defined as a composite of clinical and laboratory measures relevant to the management of CD. In addition, radiologic response was independently assessed by using modified Cheson criteria. Eighteen (78%) of 23 patients (95% CI, 56% to 93%) achieved CBR, and 12 patients (52%) demonstrated objective tumor response. All 11 patients (95% CI, 72% to 100%) treated with the highest dose of 12 mg/kg achieved CBR, and eight patients (73%) achieved objective tumor response. Overall objective-response duration ranged from 44 to > or = 889 days, and one patient had complete response for > or = 318 days. Hemoglobin increased markedly in 19 patients (median increase, 2.1 g/dL; range, 0.2 to 4.7 g/dL) in the ab...Continue Reading

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Castleman Disease

Castleman disease is a rare disorder that involves an overgrowth of cells in the lymph nodes. Unicentric Castleman disease affects one lymph node, usually in the chest or abdomen. Multicentric Castleman disease affects multiple lymph nodes, commonly located in the neck, collarbone, underarm and groin areas. Discover the latest research on Castleman disease here.

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