What is SYLVANT® (siltuximab)?

SYLVANT is the only therapy approved by the FDA for the treatment of people with multicentric Castleman disease (MCD) who are negative for human immunodeficiency virus (HIV) and human herpesvirus‑8 (HHV‑8).1,2

The National Comprehensive Cancer Network® (NCCN®) recommends using siltuximab as the first-line treatment for idiopathic multicentric Castleman disease (iMCD).3 SYLVANT is backed by the largest and most robust clinical studies in iMCD to date.1,4

SYLVANT works by neutralizing IL-6 in patients with iMCD1

SYLVANT works by binding directly to human interleukin-6 (IL-6) to prevent it from interacting with both soluble and membrane-bound IL-6 receptors.1 Increased IL-6 signaling is one of the established drivers of iMCD.5


In iMCD, excess amounts of a protein called IL-6 lead to overactivation of immune cells6,7


Abnormal IL-6 signaling may cause a cytokine storm that can lead to fever, night sweats, and unexplained weight loss, which are symptoms of iMCD8


SYLVANT was designed to target IL-6, preventing it from causing a cytokine storm and the symptoms associated with iMCD1

icon IL-6
icon Cytokines
icon Immune cells
icon IL-6 receptor
icon Cytokine storm

IL-6: An important signaling molecule that can become dysregulated in iMCD

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Overproduction of IL-6 is a common pathological driver of iMCD5

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IL-6 plays an important homeostatic role as part of the body’s immune system by regulating B cells and T cells9

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IL-6 is a cytokine that is typically produced because of an infection or tissue damage9

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IL-6 triggers B cells to produce antibodies in the germinal centers within the lymph nodes10

References: 1. SYLVANT [package insert]. Hertfordshire, UK: EUSA Pharma (UK) Ltd; 2019. 2. Mukherjee S, Martin R, Sande B, Paige JS, Fajgenbaum DC. Epidemiology and treatment patterns of idiopathic multicentric Castleman disease in the era of IL-6 directed therapy. Blood Adv. 2022;6(2):359-367. 3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V.5.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed August 15, 2022. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 4. van Rhee F, Wong RS, Munshi N, et al. Siltuximab for multicentric Castleman's disease: a randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2014;15(9):966-974. 5. van Rhee F, Voorhees P, Dispenzieri A, et al. International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease. Blood. 2018;132(20):2115-2124. 6. Fajgenbaum DC. Novel insights and therapeutic approaches in idiopathic multicentric Castleman disease. Blood. 2018;132(22):2323-2330. 7. van Rhee F, Stone K, Szmania S, Barlogie B, Singh Z. Castleman disease in the 21st century: an update on diagnosis, assessment, and therapy. Clin Adv Hematol Oncol. 2010;8(7):486-498. 8. Fajgenbaum DC, Uldrick TS, Bagg A, et al. International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease. Blood. 2017;129(12):1646-1657. 9. Garbers C, Heink S, Korn T, Rose-John S. Interleukin-6: designing specific therapeutics for a complex cytokine. Nat Rev Drug Discov. 2018;17(6):395-412. 10. Choy EH, De Benedetti F, Takeuchi T, Hashizume M, John MR, Kishimoto T. Translating IL-6 biology into effective treatments. Nat Rev Rheumatol. 2020;16(6):335-345.

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Important Safety Information

Indications and Usage

SYLVANT® (siltuximab) is 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.

Important Safety Information

Indications and Usage

SYLVANT® (siltuximab) is 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.


Severe hypersensitivity reaction to siltuximab or any of the excipients in SYLVANT.

Warnings and Precautions

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.


Do not administer live vaccines to patients receiving SYLVANT because IL-6 inhibition may interfere with the normal immune response to new antigens.

Infusion Related Reactions and Hypersensitivity

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

Gastrointestinal (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.

Adverse Reactions

The most common adverse reactions (>10% compared to placebo) in the MCD clinical trial were pruritus, increased weight, rash, hyperuricemia, and upper respiratory tract infections.

Drug Interactions

Cytochrome P450 Substrates

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).

Dosage 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 the Prescribing Information are not met, consider delaying treatment with SYLVANT. Do not reduce dose.

Do not administer SYLVANT to patients with severe infections until the infection resolves.

Discontinue SYLVANT in patients with severe infusion related reactions, anaphylaxis, severe allergic reactions, or cytokine release syndromes. Do not reinstitute treatment.

Please see full Prescribing Information for additional important safety information.