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

Abstract

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.

Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 to Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution

“…However, in patients with myelodysplastic syndrome and solid tumors like prostate cancer, ovarian cancer, and lung cancer, siltuximab as a monotherapy did not show significant clinical activity. For the treatment of patients with HIV-negative and human herpes virus-8-negative multicentric Castleman's disease, siltuximab received approval in the United States and European Union in 2014 (Chen and Chen, 2015), as treated patients showed a 5-year survival rate of 96.4% compared with 55% to 77% in those receiving standard of care treatment (Sitenga et al, 2018).…”

Monoklonale Antikörper zur antiinfektiven Therapie

“…Siltuximab ist ein humanmuriner chimärer monoklonaler Antikörper, der humanes IL‑6 bindet und 2014 von der EMA zugelassen wurde [ 36 ]. Er wird zur Therapie des Morbus Castleman, einer seltenen lymphoproliferativen Erkrankung eingesetzt [ 37 ]. Eine Kontraindikation für die Behandlung mit Siltuximab stellt eine Infektion mit HIV oder humanem Herpesvirus 8 (HHV-8) dar.…”

CTL019 (tisagenlecleucel): CAR-T therapy for relapsed and refractory B-cell acute lymphoblastic leukemia

“… 89 It is FDA-approved since 2014 for the treatment of multicentric Castleman’s Disease. 90 It is used off-label for management of CRS and, as tocilizumab, can induce rapid reversal of symptoms in most patients. 16 , 48 , 91 Even if tocilizumab is the only approved drug to treat CRS, its advantage, compared with siltuximab, remains to be proved.…”