Siltuximab has demonstrated significant efficacy and safety in patients with idiopathic multicentric
Castleman disease.[14][15] Treatment results with Siltuximab in B-cell
non-Hodgkin's lymphoma are inferior to those obtained in multicentric Castleman disease.[16] Siltuximab has also been evaluated in the treatment
ovarian cancer, however the efficacy for this cancer is debatable.[17] In addition, siltuximab has been evaluated for multiple myeloma, but there was an insignificant increase in
response rates.[18]
Side effects
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.[13]
Common
The following has been shown to occur in treatment of Multicentric
Castleman's disease with siltuximab during a clinical trial (>10% compared to placebo):[13]
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.[13]
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.[13]
^Karkera J, Steiner H, Li W, Skradski V, Moser PL, Riethdorf S, et al. (September 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): 1455–65.
doi:
10.1002/pros.21362.
PMID21321981.
S2CID32034042.
^Ferrario A, Merli M, Basilico C, Maffioli M, Passamonti F (March 2017). "Siltuximab and hematologic malignancies. A focus in non Hodgkin lymphoma". Expert Opinion on Investigational Drugs. 26 (3): 367–373.
doi:
10.1080/13543784.2017.1288213.
PMID28140696.
S2CID40363229.
^Kampan NC, Xiang SD, McNally OM, Stephens AN, Quinn MA, Plebanski M (2018). "Immunotherapeutic Interleukin-6 or Interleukin-6 Receptor Blockade in Cancer: Challenges and Opportunities". Current Medicinal Chemistry. 25 (36): 4785–4806.
doi:
10.2174/0929867324666170712160621.
PMID28707587.
S2CID30691176.