SYLVANT Clinical Data
Treatment Guidelines
Siltuximab is recommended by the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) as a preferred treatment
option for iMCD1
NCCN Guidelines® for Castleman Disease, v1.2024
aSee Criteria for Active Disease (CD-A) in the NCCN Guidelines® for more information.
bSee Diagnostic Criteria for Idiopathic MCD (CD-B) in the NCCN Guidelines® for more information.
cRituximab and hyaluronidase human injection for subcutaneous use may be substituted for rituximab after patients have received the first full dose of rituximab by intravenous infusion. This substitution cannot be made for rituximab used in combination with ibritumomab tiuxetan. An FDA-approved biosimilar is an appropriate substitute for rituximab.
dResponse assessment using the imaging modalities performed during workup (C/A/P CT with contrast or PET-CT).
eEncourage biopsy to rule out transformation to DLBCL or concomitant development of other malignancies or opportunistic infections.
fRituximab ± prednisone may repeat without limit if progression ≥6 months after completion of rituxim.
C/A/P CT, chest-abdomen-pelvis computed tomography; CD, Castleman disease; DLBCL, diffuse large B-cell lymphoma; HHV-8, human herpesvirus 8; HIV, human immunodefi ciency virus; NCCN, National Comprehensive Cancer Network; PET-CT, positron emission tomography-computed tomography.
National Comprehensive Cancer Network® (NCCN®)
Siltuximab is recommended by the NCCN Guidelines as a preferred treatment option for iMCD.
Dosage & Administration
How to administer SYLVANT.
Reference:
1. Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Guideline Name V.1.2024. © 2024 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available.
INDICATIONS AND USAGE
SYLVANT® (siltuximab) is an interleukin-6 (IL-6) antagonist indicated for the treatment of patients with multicentric Castleman’s disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative.
Limitations of Use
SYLVANT was not studied in patients with MCD who are HIV positive or HHV-8 positive because SYLVANT did not bind to virally produced IL-6 in a nonclinical study.
IMPORTANT SAFETY INFORMATION
SYLVANT is contraindicated in patients experiencing a severe hypersensitivity reaction to siltuximab or any of the excipients in SYLVANT. Hypersensitivity reactions, including anaphylactic reaction, hypersensitivity, and drug hypersensitivity have been reported in patients treated with siltuximab.
Concurrent Active Severe Infections: Do not administer SYLVANT to patients with severe infections until the infection resolves. SYLVANT may mask signs and symptoms of acute inflammation including suppression of fever and of acute Phase reactants such as C-reactive protein (CRP). Monitor patients receiving SYLVANT closely for infections. Institute prompt anti-infective therapy and do not administer further SYLVANT until the infection resolves.
Vaccinations: Do not administer live vaccines to patients or infants born to patients receiving SYLVANT because IL-6 inhibition may interfere with the normal immune response to new antigens.
Infusion Related Reactions and Hypersensitivity: SYLVANT may cause infusion-related reactions and anaphylaxis. Stop the infusion of SYLVANT if the patient develops signs of anaphylaxis. Discontinue further therapy with SYLVANT.
Stop the infusion if the patient develops a mild to moderate infusion reaction. If the reaction resolves, the SYLVANT infusion may be restarted at a lower infusion rate. Consider medicating with antihistamines, acetaminophen, and corticosteroids. Discontinue SYLVANT if the patient does not tolerate the infusion following these interventions.
Administer SYLVANT in a setting that provides resuscitation equipment, medication, and personnel trained to provide resuscitation.
Gastrointestinal (GI) Perforation: GI perforation has been reported in clinical trials although not in MCD trials. Use with caution in patients who may be at increased risk for GI perforation. Promptly evaluate patients presenting with symptoms that may be associated or suggestive of GI perforation.
The most common adverse reactions (>10% compared to placebo) during treatment with SYLVANT in the MCD clinical trial were rash, pruritus, upper respiratory tract infection, increased weight, and hyperuricemia.
To report SUSPECTED ADVERSE REACTIONS, contact Recordati Rare Diseases, Inc. at 1-888-575-8344, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Drug Interactions with Cytochrome P450 (CYP450) Substrates: Inhibition of IL-6 signaling in patients treated with SYLVANT may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment with SYLVANT.
Upon initiation or discontinuation of SYLVANT, in patients being treated with CYP450 substrates with a narrow therapeutic index, perform therapeutic monitoring of effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) as needed and adjust dose. The effect of SYLVANT on CYP450 enzyme activity can persist for several weeks after stopping therapy. Exercise caution when SYLVANT is co-administered with CYP3A4 substrate drugs where a decrease in effectiveness would be undesirable (e.g., oral contraceptives, lovastatin, atorvastatin).
Pregnancy and Lactation: SYLVANT may cause embryo-fetal harm when administered to pregnant women. Advise female patients of reproductive potential to use effective contraception during treatment with SYLVANT and for 3 months after the last dose. Advise patients not to breastfeed during treatment with SYLVANT and for 3 months after the final dose.
Pediatric Use: The safety and efficacy of SYLVANT have not been established in pediatric patients.
Dosing and Administration: Perform hematology laboratory tests prior to each dose of SYLVANT therapy for the first 12 months and every 3 dosing cycles thereafter. If treatment criteria outlined in Table 1 of the Prescribing Information are not met, consider delaying treatment with SYLVANT. Do not reduce dose.
SYLVANT® (siltuximab) for injection, for intravenous use, is available as 100 mg or 400 mg of lyophilized powder in a single-dose vial.
Please see the accompanying full Prescribing Information.
