PS1403 IDIOPATHIC MULTICENTRIC CASTLEMAN DISEASE (IMCD) IN EUROPE: A HETEROGENEOUS DISEASE TREATED WITH A VARIETY OF AGENTS
Authors: C. Hoffmann, L. Terriou, P.L. Zinzani, A. Fosså, E. Oksenhendler, M. Streetly, D. Gibson, K. Kanhai, A.G. García, L. Angenendt, S. Ferrero, J.L. Patier, S. Pierson, D. Fajgenbaum
Journal: HemaSphere (2019)

Background: Idiopathic multicentric Castleman disease (iMCD) is a rare and heterogeneous plasmacytic lymphoproliferative disorder that involves multiple regions of lymphadenopathy and cytokine‐driven systemic inflammatory symptoms. Many patients experience life‐threatening multi‐organ failure. Siltuximab, an anti‐interleukin (IL)‐6 monoclonal antibody, is the only European Medicines Agency‐approved drug treatment for iMCD based on a 34% response in a randomized phase 2 clinical trial. Better understanding of the etiology of iMCD and identification of effective treatments is urgently needed. ACCELERATE is a two‐armed natural history registry of Castleman disease (CD) comprised of a patient‐powered arm (PPA), operating out of the United States, and a physician directed arm (PDA), operating out of 9‐sites in Europe. Preliminary data from the PPA demonstrated the heterogeneity of the disease and identified dozens of off‐label drug treatments. Aims: We use the ACCELERATE registry to characterize iMCD in a European cohort and to identify the treatments most frequently used by European physicians. Methods: In the PDA, ACCELERATE consists of nine European study sites. Patients with a pathology report suggestive of Castleman disease are eligible to enroll. Site physician and study staff collect key demographic, clinical, and treatment data. Data is summarized in cases with sufficient extracted data. Quantitative data is presented as median (25 th , 75 th percentiles). Results: To date, 33 iMCD patients have met inclusion criteria (Germany 10 (30%), France 8 (24%), Italy 4 (12%), Spain 6 (18%), and Norway 5 (15%). The cohort is 48% female, and median age at diagnosis is 47.5 (38.1,57.1). Among patients with available diagnostic lymph node pathology reports (N = 22), histopathological features are strongly consistent with the histopathological characteristics defined in the 2017 International Consensus Diagnostic Criteria (Fajgenbaum et al., Blood, 2017). The most frequently noted features include interfollicular plasmacytosis (82%), vascular proliferation (68%), and atrophic germinal centers (55%). Histopathological subtypes are hyaline vascular (41%), plasmacytic (36.4%), and mixed (9.1%) with the remaining cases unspecified. Clinical and laboratory characteristics at diagnosis are also consistent with Consensus Criteria with 85% of assessed patients demonstrating constitutional symptoms, 28% organomegaly, and 19% fluid retention; laboratory abnormalities include hypoalbuminemia (33.0 (27.0, 35.0) g/L), inflammation (CRP 115.0 (12.2, 127.0) mg/L), anemia (hemoglobin 10.1 (8.5,12.1) g/dL), and hypergammaglobulinemia (17.3 (10.1, 33.4) g/L)). In this cohort, twenty unique drugs have been used to treat iMCD, including antineoplastic agents, corticosteroids, immunosuppressive agents, anti‐IL6 therapy, and immunoglobulins. Rituximab and siltuximab are the most frequently administered drugs, administered to 50% and 39% of treated patients, respectively Summary/Conclusion: European iMCD patients in the ACCELERATE registry demonstrate clinical, laboratory, and pathological features consistent with iMCD found in other regions of the world. Despite there only being one EMA‐approved therapy for iMCD, many other agents are being used off‐label. Rituximab is the most frequently administered drug in patients in both the US and European centers, and siltuximab is among the top three drugs across both arms of the registry. Data collection is ongoing, and further work and additional patients are needed to assess the effectiveness of treatments in this cohort.