UNDERSTANDING iMCD
About iMCD
Castleman disease (CD) is a heterogeneous group of rare disorders1
The two primary types of CD are unicentric and multicentric, which include a wide range of etiologies, presentations, treatments, and outcomes.2,3
Multicentric CD (MCD) is a subset of CD that has lymphadenopathy in multiple lymph node sites and is further divided into subsets classified by an underlying driver, including2,3:
While the underlying etiology of iMCD is currently unknown, it is a rare and potentially life-threatening, yet treatable, disorder affecting all populations.2
aAlso known as Kaposi sarcoma–associated herpesvirus.2
HHV-8, human herpesvirus-8; HIV, human immunodeficiency virus, POEMS, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes.
iMCD is a potentially life-threatening condition that can hide in the shadows of other diseases2
Due to the overlapping symptoms and rarity of the disorder, diagnosing iMCD can be challenging.2
iMCD can mimic the characteristics of autoimmune, malignant,
and infectious disorders*2,4,5
Adapted from Fajgenbaum et al.2
© Elsevier Inc. Fajgenbaum et al. Blood. 2017;129(12):1646-1657. Reprinted with permission.
DID YOU KNOW?
In the United States alone, more than 1,000 people per year are diagnosed with iMCD.4*
iMCD is not an “indolent disease”6†
iMCD is associated with increased rates of morbidity6†
Emerging results demonstrate significantly higher rates of morbidity in patients with iMCD compared to a control population6†
Morbidities frequently observed in patients with iMCD (P<0.05)7†
Clinical Presentation
Specific symptoms, dysfunctions, and other manifestations collectively contribute to the hallmarks that indicate iMCD.
References:
1. 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. 2. 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. 3. Dispenzieri A, Fajgenbaum DC. Overview of Castleman disease. Blood. 2020;135(16):1353-1364. 4. 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. 5. 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. 6. Mukherjee S, Kanhai K, Kauffman D, et al. Organ dysfunction, thrombotic events and malignancies in patients with idiopathic multicentric Castleman disease: a population-level US health claims analysis. Leukemia. 2022;36(10):2539-2543. 7. Mukherjee S, Kanhai K, Kauffman D, et al. Non-hematological malignancies in idiopathic multicentric Castleman disease patients: a matched cohort analysis using a health claims-based dataset. Poster presented at: European Hematology Association (EHA) Congress; June 9-12, 2022; Vienna, Austria. Poster P1733.
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.
