Long-term efficacy with SYLVANT® (siltuximab)1

Disease control was defined as “stability or improvement and no worsening in hemoglobin, fatigue, anorexia, fever, weight, and size of the largest lymph node.”

Durable Disease Control With SYLVANT (N=60)a

97%(n=58)

Disease control at last on-study assessmentb

70%(n=42)

Disease control for up to 6 yearsc

Over 6 years, patients may have missed or rescheduled a dose for multiple personal or physician directed reasons. Some patients may not have received the recommended dose (11 mg/kg, every 3 weeks).

Some of these patients discontinued before the 6-year data cutoff point while others were not dosed at 3 weeks.

Patients completed the trial up to the 6-year data cutoff point.

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This study confirmed the proven efficacy and safety in patients with iMCD who started and stayed on SYLVANT.1

Patients should stay on SYLVANT until disease progression2

In a SYLVANT clinical trial, a durable response rate was defined as tumor and symptomatic response that persisted for a minimum of 18 weeks without treatment failure.3

The CDCN established assessment criteria for evaluating response to treatment, taking into account all features of iMCD. These include2:

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Objective biochemical markers of inflammatory response and organ function (hemoglobin, CRP, albumin, GFR)
Response Evaluation: Monthly
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Lymph node size
Response Evaluation: First recommended at 6 weeks and at 3-month intervals thereafter until maximum regression
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Clinical symptoms (fatigue, anorexia, fever, weight change) as assessed by the clinician
Response Evaluation: Monthly

Complete response requires normalization of biochemical markers, lymph node response by CT scan, and improvements in clinical symptoms.2

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In patients treated with anti-IL-6 treatments, lymph node response may take several months.2

Infusion-related reactions and hypersensitivity3

  • If your patient has a mild to moderate infusion reaction or an allergic reaction while receiving SYLVANT, you must stop the infusion and treat their reaction. If the reaction resolves, then treatment with SYLVANT can be restarted at a lower infusion rate

  • If your patient has a severe infusion or allergic reaction, you must stop the treatment with SYLVANT completely

Abbreviations: CDCN, Castleman Disease Collaborative Network; CRP, C-reactive protein; CT, computed tomography; GFR, glomerular filtration rate; IL-6, interleukin 6; iMCD, idiopathic multicentric Castleman disease.

Post hoc analysis: Assessing response to SYLVANT4

A post hoc analysis was conducted in patients who achieved the primary end point of durable tumor and symptomatic response in the pivotal phase 2 trial of siltuximab.

Following are the details about time to normalization of parameters in SYLVANT responders (n=18):

Post hoc analysis Sylvant

aNormalized defined as ≤ upper limit of normal.

b≥50% reduction in a 34-point symptom score from baseline.

cTimes to normalization were not significantly different between the 2 treatment arms.

dNormalized defined as ≥ lower limit of normal.

e≥50% decrease in the sum of the product of the diameters from baseline.

fMaintained for at least 18 weeks.

Abbreviation: IgG, immunoglobulin G.

Early indicators of response to SYLVANT included improved thrombocytosis and symptomatic responses, which occurred as early as 1 month after starting SYLVANT. Biochemical responses were also seen within 3 months of starting SYLVANT in the majority of responders.

Lymph node responses are slower to show improvements and should not be used to drive early treatment decisions after starting SYLVANT.

Limitations: Since the evidentiary value of post hoc analyses is less than that of primary or secondary analyses, cautious interpretation of these data is advised. Presentation of these data is not intended to represent additional treatment effects of the drug.

References: 1. van Rhee F, Casper C, Voorhees PM, et al. Long-term safety of siltuximab in patients with idiopathic multicentric Castleman disease: a prespecified, open-label, extension analysis of two trials. Lancet Haematol. 2020;7(3):e209-e217. 2. 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. 3. SYLVANT [package insert]. Hertfordshire, UK: EUSA Pharma (UK) Ltd; 2019. 4. van Rhee F, Rosenthal AL, Kanhai K, et al. Siltuximab is associated with improved progression-free survival in idiopathic multicentric Castleman disease. Blood Adv. Published ahead of print July 6, 2022. doi:10.1182/bloodadvances.2022007112

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SYLVANT® (siltuximab) for injection

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.

SYLVANT® (siltuximab) for injection

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.

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 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.

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

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).

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 females not to breastfeed during treatment with SYLVANT and for 3 months after the final dose.

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

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.

Before prescribing SYLVANT, please read the full Prescribing Information.

For your idiopathic multicentric Castleman disease (iMCD) Patients Taking SYLVANT® (siltuximab)

R.A.R.E.® can help

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  • Prior Authorization and Appeals Support:
    Phone: 1-855-299-8844
    Fax: 1-888-223-1746

One on one support

Helga will call enrolled patients to help:

  • Educate and answer questions about iMCD and SYLVANT
  • Help with access to SYLVANT medication
  • Connect them with other iMCD educational resources
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