Impact of siltuximab on patient-related outcomes in multicentric Castleman's disease

Multicentric Castleman's disease (MCD) is a rare, widespread lymphoproliferative disorder and a life-threatening disease involving hyperactivity of the immune system, excessive proinflammatory cytokine release, immune cell proliferation, and organ system dysfunction. Interleukin-6 (IL-6) is a cytokine that plays a key role in the pathogenesis of MCD, as it is involved in the synthesis of acute-phase reactants and aids in the induction of B-cell proliferation. Siltuximab is an anti-IL-6 chimeric monoclonal antibody that acts as a novel treatment modality to bind to IL-6 with high affinity, thus neutralizing the cytokine bioactivity and inhibiting B-cell proliferation. Clinical trials with siltuximab have shown early clinical promise for patients with MCD for many years, leading to recent US Food and Drug Administration approval as a novel agent for the treatment of MCD. Here, a systematic review was conducted to include 171 cases of MCD patients treated with siltuximab. While traditional treatment methods were able to achieve a 5-year survival rate of only 55%-77%, results of siltuximab treatment demonstrated 5-year survival rates of nearly 96.4% (only 2 deaths reported out of 55 patients with follow-up data). Ultimately, the results from multiple clinical trials have demonstrated that siltuximab is extremely efficacious in alleviating disease symptoms (fatigue, pain, and lymphadenopathy) while simultaneously achieving disease remission, thus extending progression-free survival for years longer than the average 5-year survival rates for MCD.