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About CD / iMCD

Castleman Disease (CD)

Castleman disease refers to a heterogenous group of disorders that share histopathological features of the lymph nodes.

  • Despite the shared histopathological features, these disorders have a wide range of etiologies, presentations, treatments and outcomes1,2
  • Multicentric Castleman disease (MCD) is a subset of CD which presents with lymphadenopathy in multiple lymph node sites, and is further divided into three subsets1,2:
    • Human herpesvirus-8 positive MCD (HHV-8+ MCD)
    • POEMS-MCD (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes)
    • Idiopathic MCD (iMCD) with unknown etiology

Abbreviations: CD, Castleman disease; HHV-8, human herpesvirus-8; iMCD, idiopathic multicentric Castleman disease; MCD, Multicentric Castleman disease; POEMS, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes; UCD, unicentric Castleman disease.
References: 1. 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. 2. Dispenzieri A, Fajgenbaum DC. Overview of Castleman disease. Blood. 2020;135(16):1353-1364.

Diagram showing information about Castleman Disease
  • Introduction
  • Prognosis
  • Potential causes
  • Diagnosis

Idiopathic multicentric Castleman disease (iMCD) – Introduction

iMCD is a rare disorder that could potentially be life-threatening. In a retrospective analysis in the the US, the annual incidence of iMCD was 3.1–3.4 cases per million. In the same study, the prevalence of iMCD was estimated at 6.9–9.7 cases per milllion.1*

*Study Methodology1
A retrospective claims-based analysis evaluated the burden of illness using Truven MarketScan® data in the US from 2006-2020. Out of 30.7 million eligible patients, 254 were identified as having iMCD based on diagnosis code and ≥2 minor diagnostic and lab criteria.

The incidence of iMCD likely reflects individuals with a new diagnosis, and the prevalence of iMCD likely reflects individuals with a diagnosis currently listed in their medical record. Patients with claims associated with the ICD-9 code before 2017 were not included in incidence calculations.

Limitations
The data from this analysis is retrospective and has less evidentiary value than prospective studies. The study uses health claims datasets, which lack histopathology confirmation and detailed clinical documentation, are subject to coding and data entry errors, and thus results cannot be generalized to the full U.S. patient population.

This research was sponsored by EUSA Pharma now owned by Recordati Rare Diseases Inc. One of its employees participated in the analysis and interpretation of data.

Abbreviations: iMCD, idiopathic multicentric Castleman disease; NOS, not otherwise specified; US, United States; TAFRO, thrombocytopenia, anasarca, fever, reticulin fibrosis, organomegaly.
References: 1. 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. 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.
Chart showing information about iMCD

Abbreviations: iMCD, idiopathic multicentric Castleman disease; NOS, not otherwise specified; US, United States; TAFRO, thrombocytopenia, anasarca, fever, reticulin fibrosis, organomegaly.
References: 1. 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. 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.

Idiopathic multicentric Castleman disease (iMCD) – Prognosis

iMCD requires timely diagnosis and treatment at the point of diagnosis to support best possible outcomes.

  • iMCD is a chronic disease that can progress in the absence of treatment and can lead to severe comorbidities and death.1–3
  • Patients with iMCD have poorer outcomes than many cancers, including Stage II colon cancer, Stage III breast cancer, and progressive non‑Hodgkin lymphoma.4
  • In a retrospective analysis of US claims data, a higher proportion of patients with iMCD presented with organ failure and/or thrombotic events, compared with a non-iMCD matched cohort.5*
  • The same analysis found that patients with iMCD had higher prevalence of several malignancies, compared with a non-iMCD matched cohort.5*
*Study Methodology5
A retrospective claims-based analysis evaluated the burden of illness using Truven MarketScan® data in the US from 2006-2020. Out of 30.7 million eligible patients, 271 were identified as having iMCD based on diagnosis code and ≥2 minor diagnostic and lab criteria. Key morbidities and healthcare metrics were analyzed using iMCD patients matched with non-iMCD controls.

Limitations
The data from this analysis is retrospective and has less evidentiary value than prospective studies. The study uses health claims datasets, which lack histopathology confirmation and detailed clinical documentation, are subject to coding and data entry errors, and thus results cannot be generalized to the full U.S. patient population.

This research was sponsored by EUSA Pharma now owned by Recordati Rare Diseases Inc. Some of its employees participated in the analysis and interpretation of data.

Abbreviations: iMCD, idiopathic multicentric Castleman disease.
References: 1. 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. 2. Fajgenbaum DC. Novel insights and therapeutic approaches in idiopathic multicentric Castleman disease. Blood. 2018;132(22):2323-2330. 3. Yu L, Tu M, Cortes J, et al. Clinical and pathological characteristics of HIV- and HHV-8-negative Castleman disease. Blood. 2017;129(12):1658-1668. 4. Sitenga J, Aird G, Ahmed A, Silberstein PT. Impact of siltuximab on patient-related outcomes in multicentric Castleman's disease. Patient Relat Outcome Meas. 2018;9:35-41. 5. 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. 202;36(10):2539-2543.
Chart showing information about the long-term progressive disease

Abbreviations: iMCD, idiopathic multicentric Castleman disease.
References: 1. 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. 2. Fajgenbaum DC. Novel insights and therapeutic approaches in idiopathic multicentric Castleman disease. Blood. 2018;132(22):2323-2330. 3. Yu L, Tu M, Cortes J, et al. Clinical and pathological characteristics of HIV- and HHV-8-negative Castleman disease. Blood. 2017;129(12):1658-1668. 4. Sitenga J, Aird G, Ahmed A, Silberstein PT. Impact of siltuximab on patient-related outcomes in multicentric Castleman's disease. Patient Relat Outcome Meas. 2018;9:35-41. 5. 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. 202;36(10):2539-2543.

Idiopathic multicentric Castleman disease (iMCD) – Potential causes

The idiopathic form of CD has no known cause.

  • Unlike other lymphoproliferative disorders, a dysregulated overproduction of interleukin-6 (IL-6) is a common pathological driver of iMCD and its symptoms.1,2
  • In severe cases, a life-threatening cytokine storm can occur, followed by organ failure and death.2

Abbreviations: iMCD, idiopathic multicentric Castleman disease; IL-6, interleukin-6; VEGF, vascular endothelial growth factor.
References: 1. 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. 2. 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 Hem & Onc. 2010;8:486–98.

Chart showing information about Increased IL–6 activity

Abbreviations: iMCD, idiopathic multicentric Castleman disease; IL-6, interleukin-6; VEGF, vascular endothelial growth factor.
References: 1. 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. 2. 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 Hem & Onc. 2010;8:486–98.

Idiopathic multicentric Castleman disease (iMCD) – Diagnosis

Undiagnosed idiopathic multicentric Castleman disease (iMCD) patients exhibit a wide spectrum of possible symptoms.

  • There is no ‘typical’ iMCD patient and undiagnosed patients have a range of possible symptoms which will see them under the care of a variety of specialists, e.g., hematologists, rheumatologists, immunologists.1
  • Patients are usually referred for an (excisional) lymph node biopsy by their clinician, who has noticed symptoms that require further investigation.1

Abbreviations: ALPS, autoimmune lymphoproliferative syndrome; AOSD, adult-onset Still disease; EBV, Epstein-Barr virus; FDC, follicular dendritic cell; HHV-8, human herpesvirus-8; HL, Hodgkin lymphoma; HLH-MAS, hemophagocytic lymphohistiocytosis macrophage activation syndrome; IgG4, IgG4-related disease; iMCD, idiopathic multicentric Castleman disease; JIA, juvenile idiopathic arthritis; M-HLH, malignancy associated hemophagocytic lymphohistiocytosis; NHL, non‑Hodgkin lymphoma; POEMS, polyneuropathy, organomegaly, endocrinopathy, monoclonal paraprotein, skin changes; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; V-HLH, viral hemophagocytic lymphohistiocytosis.
References: 1. 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.

Chart showing information about the diagnosis of iMCD

Abbreviations: ALPS, autoimmune lymphoproliferative syndrome; AOSD, adult-onset Still disease; EBV, Epstein-Barr virus; FDC, follicular dendritic cell; HHV-8, human herpesvirus-8; HL, Hodgkin lymphoma; HLH-MAS, hemophagocytic lymphohistiocytosis macrophage activation syndrome; IgG4, IgG4-related disease; iMCD, idiopathic multicentric Castleman disease; JIA, juvenile idiopathic arthritis; M-HLH, malignancy associated hemophagocytic lymphohistiocytosis; NHL, non‑Hodgkin lymphoma; POEMS, polyneuropathy, organomegaly, endocrinopathy, monoclonal paraprotein, skin changes; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; V-HLH, viral hemophagocytic lymphohistiocytosis.
References: 1. 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.