Epidemiology and clinical characteristics of idiopathic multicentric castleman disease in Spain (ARCANA study): Prevalence cohort

Abstract

Abstract Background Idiopathic multicentric Castleman disease (iMCD) is a rare, heterogeneous lymphoproliferative disorder affecting multiple lymph nodes, causing systemic inflammation, cytopenias, and potentially life-threatening multiorgan dysfunction. Diagnosing and managing iMCD is challenging, requiring a multidisciplinary approach. Advances in the treatment have highlighted the role of IL-6 in its pathogenesis. The absence of consensus diagnostic criteria until 2017, specific biomarkers, low incidence and variable response criteria, complicate its diagnosis and treatment evaluation. Additionally, its clinical overlap with malignancies, autoimmune diseases, and infections, along with its heterogeneous presentation can lead to misdiagnosis. Despite of recent treatment advances the prognosis is still poor in a subset of patients. Epidemiologic data on iMCD is limited in Western countries. To address this lack of information, the first Spanish iMCD registry was proposed to increase the knowledge on the prevalence and incidence of this rare disease. Aim The main objective was to assess the prevalence and incidence of iMCD in Spain. This registry will increase the knowledge on the epidemiology, demographics, clinical features, and treatment outcomes of iMCD in Spain. Methods This is a multicenter observational study of iMCD, which aimed to enroll patients from 20 centers across Spain and comprises two cohorts: Prevalence cohort (PC): historical cases of iMCD patients, and Incidence cohort (IC): newly diagnosed iMCD patients identified during the recruitment period and followed prospectively. Demographic data, clinical characteristics, pathology patterns and type of treatment were retrieved from the records of each center by the local investigators. Cases were then reviewed by a panel of three experts to assess the diagnosis of iMCD. Prevalence was calculated as the total number of diagnosed iMCD cases under follow-up at the time of the site initiation visit, and as the denominator, the reference population of the centers participating in the study (5,915,367). Results From February 2023 to July 2025, 47 patients have been enrolled, with 35 meeting the inclusion criteria: 30 in the PC and 5 in the IC (three additional patients are currently being evaluated for potential inclusion in the IC). The remaining 9 individuals (7 PC and 2 IC) were excluded because they did not meet the diagnostic criteria of iMCD. Preliminary results from the prevalence cohort include 30 patients from 15 Spanish hospitals. Twenty-three patients (76.7%) had iMCD NOS and 7 (23.3%) fulfilled criteria of TAFRO. Median age was 47 years (range: 42, 60), with an equal gender distribution (50% female and 50% male). Regarding ethnicity, 76.7% of patients were Caucasian, followed by Latin (10.0%), Black (6.7%), Asian (3.3%), and Arab (3.3%). Twenty-one patients (70%) had at least one comorbid condition, being present in 18 patients (60%) at the time of iMCD. The most common comorbidities were hypertension (n=7) and autoimmune disorders (n=6). One case of a thrombotic event (superior vena cava thrombus, 4.8%) presented in a patient after iMCD diagnosis. No hematological neoplasms were described but two cases of non-hematological neoplasms were reported: one squamous cervical intraepithelial neoplasia (4.8%) and one benign prostatic hypertrophy (4.8%). Regarding the pathology subtype, 13 (43.3%) were plasmacytic, 4 (13.3%) hypervascular, and 10 (33%) mixed. At study entry, 73.3% had received prior treatments (median of 2 lines, range 1-7). Currently, 21 patients are on treatment with siltuximab (90,4%), 1 with sirolimus (4.8%) and 1 with tocilizumab (4.8%). Most patients (93.3%) had a good response to the last line of treatment: achieving complete response (11, 36.7%), partial response (9, 30%), or stable disease (8, 26.7%), with only 2 (6.7%) in progression. The estimated iMCD prevalence was 0.50715 cases per 100.000 inhabitants (95% CI: 0,32567-0,68863). Conclusions An important number of patients were excluded because they did not meet iMCD diagnostic criteria. The prevalence of iMCD in Spain is very low and similar to that reported from other geographical areas. Hypertension and autoimmune disorders were the most common comorbidities. IL-6 blockade is currently the most common therapeutic approach and the majority of patients have a favorable response to standard therapy.