|Chemical and physical data|
|Molar mass||145.0 kg/mol|
|(what is this?)|
Siltuximab (INN, trade name Sylvant; also known as CNTO 328, anti-IL-6 chimeric monoclonal antibody or cCLB8) is a chimeric (made from human and mouse proteins) monoclonal antibody. It binds to interleukin-6. Siltuximab has been investigated for the treatment of neoplastic diseases: metastatic renal cell cancer, prostate cancer, and Castleman's disease, among other types of cancer.
It has undergone a phase I clinical trial in patients With B-cell non-Hodgkin's lymphoma, multiple myeloma, or Castleman's disease. There were encouraging results in a small trial for advanced ovarian cancer.
Encouraging results have been reported from a phase II trial for relapsed or refractory multiple myeloma.
On April 23, 2014, siltuximab was FDA approved under the brand name of Sylvant for the treatment of patients with multicentric Castleman’s disease (MCD) who do not have human immunodeficiency virus (HIV) or human herpesvirus-8 (HHV-8).
A randomized double-blind placebo controlled trial demonstrated that siltuximab treatment improved symptomatic multicenric Castleman’s disease (MCD) compared to placebo. Primary endpoints in the study included durable tumor and symptomatic response defined as complete or partial response with improvement or stabilization of disease related symptoms for at least 18 weeks.
A total of 79 patients were enrolled in the study (53 assigned to siltuximab, 26 assigned to placebo. This study included HIV-negative and human herpevisrus 8 (Kaposi's sarcoma-associated herpesvirus) seronegative patients aged 20–78 years old with symptomatic multicentric Castleman’s disease (fatigue, malaise, night sweats, peripheral sensory neuropathy, anorexia, pruritus, dyspnea, oedma, hyperhidrosis) 
Siltuximab may lower resistance to infections and should not be administered to patients with severe infections. Siltuximab should be discontinued in patients with severe infusion related reactions, anaphylaxis, severe allergic reactions or cytokine release syndromes. Live vaccines should not be administered to patients receiving siltuximab since IL-6 inhibition may interfere with normal immune response to new antigens.
- Peripheral edema
- Abdominal Pain
- Increased weight
- Upper respiratory tract infections
Long term exposure
Siltuximab may increase CYP450 activity leading to increased metabolism of drugs that are CYP450 substrates. Co-administration of siltuximab and CYP450 substrates with narrow therapeutic index such as warfarin, ciclosporin or theophylline should be closely monitored.
Mechanism of action
Siltuximab is a chimeric monoclonal antibody that binds to interleukin-6 (IL-6), preventing binding to soluble and membrane bound interleukin-6 receptors. Siltuximab interferes with IL-6 mediated growth of B-lymphocytes and plasma cells, secretion of vascular endothelial growth factor (VEGF) and autoimmune phenomena.
- International Nonproprietary Names for Pharmaceutical Substances (INN, prepublication copy), World Health Organization.
- Siltuximab mechanism of action
- Korneev, KV; Atretkhany, KN; Drutskaya, MS; Grivennikov, SI; Kuprash, DV; Nedospasov, SA (January 2017). "TLR-signaling and proinflammatory cytokines as drivers of tumorigenesis.". Cytokine. 89: 127–135. PMID 26854213. doi:10.1016/j.cyto.2016.01.021.
- Rossi, J. -F.; Négrier, S.; James, N. D.; Kocak, I.; Hawkins, R.; Davis, H.; Prabhakar, U.; Qin, X.; Mulders, P.; Berns, B. (2010). "A phase I/II study of siltuximab (CNTO 328), an anti-interleukin-6 monoclonal antibody, in metastatic renal cell cancer". British Journal of Cancer. 103 (8): 1154–1162. PMC . PMID 20808314. doi:10.1038/sj.bjc.6605872.
- Karkera, J.; Steiner, H.; Li, W.; Skradski, V.; Moser, P. L.; Riethdorf, S.; Reddy, M.; Puchalski, T.; Safer, K.; Prabhakar, U.; Pantel, K.; Qi, M.; Culig, Z. (2011). "The anti-interleukin-6 antibody siltuximab down-regulates genes implicated in tumorigenesis in prostate cancer patients from a phase I study". The Prostate. 71 (13): 1455–1465. PMID 21321981. doi:10.1002/pros.21362.
- Van Rhee, F.; Fayad, L.; Voorhees, P.; Furman, R.; Lonial, S.; Borghaei, H.; Sokol, L.; Crawford, J.; Cornfeld, M.; Qi, M.; Qin, X.; Herring, J.; Casper, C.; Kurzrock, R. (2010). "Siltuximab, a Novel Anti-Interleukin-6 Monoclonal Antibody, for Castleman's Disease". Journal of Clinical Oncology. 28 (23): 3701–3708. PMID 20625121. doi:10.1200/JCO.2009.27.2377.
- First IL-6–blocking drug nears approval for rare blood disorder Nature Medicine, October 7, 2013
- ClinicalTrials.gov: Siltuximab
- "A Safety and Efficacy Study of CNTO 328 in Patients With B-Cell Non-Hodgkin's Lymphoma, Multiple Myeloma, or Castleman's Disease".
- "CNTO 328 Shows Promise For Ovarian Cancer In Small Clinical Trial, Say U.K. Scientists.". 2009.
- "A phase II multicenter study of CNTO 328, an anti-IL-6 monoclonal antibody, in patients (pts) with relapsed or refractory multiple myeloma (MM)". 2009.
- Sylvant official website
- FDA.gov press release for siltuximab approval, accessed April 24, 2014
- Siltuximab cancer regimen & references
- "Sylvant Prescribing Information" (PDF). janssenmd. Retrieved 3 November 2014.
- Van Rhee, F; Wong, R; Nikhil, M; Rossi, J; Ke, X; Fossa, A; Simpson, D; Capra, M; Liu, T; Hsieh, RK; Goh, YT; Zhu, J; Cho, SG; Ren, H; Cavet, J; Rajesh, B; Rothman, M; Puchalski, TA; Reddy, M; van de Velde, H; Vermeulen, J; Casper, C (July 18, 2014). "Siltuximab for multi centric Castleman's disease: a randomised, double-blind, placebo-controlled trial". Lancet Oncology. 15: 966–974. PMID 25042199. doi:10.1016/S1470-2045(14)70319-5.