SYLVANT Clinical Data
Post-Hoc Analysis
In a post-hoc analysis, SYLVANT® (siltuximab) showed durable symptomatic response and increased time to treatment failure1,2
Response to SYLVANT was greater when both major and at least 2 minor criteria were met3,c
Additional efficacy analysis was performed by retrospectively applying the minor criteria to the SYLVANT-treated patients from the pivotal clinical trial.1,3
n represents the total number of patients treated with SYLVANT who met the major criteria and at least that number of minor criteria including ≥ 1 laboratory abnormality.
BSC, best supportive care; ITT, intent to treat; NR, not reached.
This post-hoc analysis was not adequately powered nor error-controlled for subgroup analyses.
Treatment differences observed in this subgroup cannot be regarded as statistically significant and therefore no conclusions should be drawn.
Limitations: This is a post-hoc analysis. The data should be considered descriptive only and no conclusions can be drawn. 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.
cResponse to SYLVANT was evaluated according to the NCT01024036 primary endpoint (decrease in lymph node size as per modified Cheson criteria in the absence of symptom progression) for the 54 of 79 patients randomized to the SYLVANT arm.3
A post-hoc analysis also analyzed progression-free survival (PFS) and overall survival (OS)2
This is a post-hoc analysis. The data should be considered descriptive only and no conclusions can be drawn.
DID YOU KNOW?
Despite recent advances, iMCD remains a serious condition with poor prognosis5,6
- iMCD has a worse prognosis than many cancers4, with 5-year overall survival (OS) estimated to be 74% to 84%5,6
- Prior to the introduction of IL-6 targeted therapy, 35% to 60% of patients with iMCD died within 5 and 10 years after diagnosis, respectively4
- The improvement in survival rates can be attributed to several factors, including the establishment of formal diagnostic criteria, the approval of targeted IL-6 therapies, and the development of comprehensive treatment guidelines3,7
- Early targeted treatment is essential to control immune dysregulation and improve outcomes in patients with iMCD4
Treatment Guidelines
Siltuximab recommended as preferred treatment.
References:
1. 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. 2. van Rhee F, Rosenthal A, Kanhai K, et al. Siltuximab is associated with improved progression-free survival in idiopathic multicentric Castleman disease. Blood Adv. 2022;6(16):4773-4781. 3. 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. 4. van Rhee F, Rosenthal A, Kanhai K, et al.Siltuximab is associated with improved progression-free survival in idiopathic multicentric Castleman disease. Blood Adv. 2022;6(16):4773-4781. Published correction appears in Blood Adv. 2023;7(8):1604-1605. 5. Cohen, Aaron B, et al. “Clinical characteristics, treatment trends, and outcomes of patients with HHV-8-negative/idiopathic multicentric Castleman disease treated with siltuximab in a machine learning-selected real-world cohort.” Blood. 2023; 142 (Supplement 1): 907.
6. Liu W, Cai Q, Yu T, et al. Clinical characteristics and outcomes of Castleman disease: a multicenter consortium study of 428 patients with 15-year follow-up. Am J Cancer Res. 2022;12(9):4227-4240. 7. van Rhee F, Voorhees P, Dispenzieri A, et al. International, evidence-based consensus treatment guidelines for idiopathic multicentric Castlemen disease. Blood. 2018;132(20):2125-2124.
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.
