A Novel Predictive Model for Idiopathic Multicentric Castleman Disease: The International Castleman Disease Consortium Study

Abstract

Background Patients with multicentric Castleman disease (MCD) who are negative for human immunodeficiency virus and human herpesvirus 8 are considered to have idiopathic MCD (iMCD). The clinical presentation of iMCD varies from mild constitutional symptoms to life‐threatening symptoms or death. The treatment strategy varies from “watchful waiting” to high‐dose chemotherapy. This diverse clinical presentation calls for a classification stratification system that takes into account the severity of the disease. Subjects, Materials, and Methods We analyzed the clinical, laboratory, and pathologic abnormalities and treatment outcomes of 176 patients with iMCD (median follow‐up duration 12 years) from the U.S. and China to better understand the characteristics and prognostic factors of this disease. This discovery set of iMCD results was confirmed from the validation set composed of additional 197 patients with iMCD organized from The International Castleman Disease Consortium. Results Using these data, we proposed and validated the iMCD international prognostic index (iMCD‐IPI), which includes parameters related to patient characteristics (age > 40 years), histopathologic features (plasma cell variant), and inflammatory consequences of iMCD (hepatomegaly and/or splenomegaly, hemoglobin <80 g/L, and pleural effusion). These five factors stratified patients according to their performance status and extent of organ dysfunction into three broad categories: low risk, intermediate risk, and high risk. The iMCD‐IPI score accurately predicted outcomes in the discovery study cohort, and the results were confirmed on the validation study cohort. Conclusion This study represents the largest series of studies on patients with iMCD in the field and proposed a novel risk‐stratification model for iMCD‐IPI that could be used to guide risk‐stratified treatment strategies in patients with iMCD. Implications for Practice Patients with idiopathic multicentric Castleman disease (iMCD) can benefit from care based on clinical symptoms and disease severity. This study in 176 patients with iMCD constructed an iMCD‐IPI score based on five clinical factors, including age >40 years, plasmacytic variant subtype, hepatomegaly and/or splenomegaly, hemoglobin <80 g/L, and pleural effusion, and stratified patients into three risk categories: low risk, intermediate risk, and high risk. The predictive value was validated in an independent set of 197 patients with iMCD from The International Castleman Disease Consortium. The proposed novel model is valuable for predicting clinical outcome and selecting optimal therapies using clinical parameters.

Idiopathic Multicentric Castleman Disease

“…Treatment responses are evaluated based on CDCN criteria which include biochemical (decreased CRP, improvement of anemia and hypoalbuminemia), lymph node (regression on follow up imaging) and symptomatic resolution. Poor prognostic factors in these patients are age greater than 40 years, PC variant, and the presence of systemic signs such as anemia, pleural effusion, and hepatosplenomegaly [16].…”

The management of Castleman disease

“…46 Similar to the approach used in the 2018 consensus guidelines, the iMCD International Prognostic Index (iMCD-IPI) has recently sought to stratify patients according to performance status and organ dysfunction to predict response to therapy. 48 In iMCD, CRP concentration closely correlated with IL-6 and may be used to track activity and treatment response. 49 A suggested treatment algorithm for iMCD-NOS is shown in Figure 2.…”

“…46 The choice of treatment is driven primarily by the urgency for a symptomatic response, rather than histopathological characteristics. 47,48 The burden of symptoms in severe cases may be defined as those with at least two of the following: ECOG PS score of ≥2; severe renal impairment (glomerular filtration rate <30 ml/min/1.73 m 2 ); widespread serous effusions; haemoglobin <80 g/l and pulmonary involvement including pneumonitis. 46 Similar to the approach used in the 2018 consensus guidelines, the iMCD International Prognostic Index (iMCD-IPI) has recently sought to stratify patients according to performance status and organ dysfunction to predict response to therapy.…”

Multicentric Castleman's disease. Symptoms, diagnostics and therapy

“…Mezi oběma formami existuje kontinuální vývoj. A tak se inovace léčebných doporučení možná bude v dalších letech odvíjet od prognostického indexu, který byl publikován v roce 2020 a je uveden v tabulce 6 (27,28). Pro účely klinických studií jsou definovány i léčebné odpovědi (20).…”