Recordati Presents Breakthrough AI Technology and Real-World Evidence for Castleman Disease at ASH 2025
核心洞察
Recordati Rare Diseases presented four studies at ASH 2025 showcasing advances in Castleman disease (搜索) understanding, including the first AI-based histopathology grading model for automated diagnosis.
The BURDEN-iMCD study revealed that patients with idiopathic multicentric Castleman disease (搜索) have 6.9-fold higher morbidity rates and 7.61-fold higher healthcare costs compared to matched controls.
Pediatric analysis from the ACCELERATE registry showed children with iMCD experience more severe disease than adults but respond similarly to siltuximab treatment.
Recordati Rare Diseases presented groundbreaking research at the 67th American Society of Hematology Annual Meeting in Orlando, showcasing four studies that advance understanding of Castleman disease (搜索) (CD), a group of rare immune system disorders characterized by abnormal lymph node enlargement and systemic inflammatory symptoms. The presentations highlight significant developments in artificial intelligence-driven diagnosis, real-world disease burden analysis, pediatric disease characteristics, and subtype classification.
AI-Powered Diagnostic Innovation
Researchers unveiled the first proof-of-concept machine learning model for recognizing and grading Castleman-like histology features, representing a major advancement in diagnostic capabilities. The attention-based multiple-instance learning model automatically scores CD tissue samples, with performance evaluated against expert consensus among eight board-certified hematopathologists.
"To our knowledge, this is the first study to show the feasibility of using an attention-based artificial intelligence model to automatically score key histologic features in Castleman disease (搜索)," commented principal investigator Robert S. Ohgami, MD, PhD, Professor of Pathology at the University of Utah. "We hope this model, once optimized, will enable faster, more accurate, and more consistent diagnosis of Castleman disease."
Substantial Disease and Economic Burden Revealed
The BURDEN-iMCD study analyzed administrative claims data from the Merative MarketScan Databases spanning January 2016 through June 2024, comparing 140 patients with idiopathic multicentric Castleman disease (搜索) (iMCD) to 420 matched controls. The retrospective analysis documented a 6.9-fold higher prevalence of morbidities (95% confidence interval: 6.7, 7.2) across multiple clinical domains, including anemia (搜索), renal dysfunction (搜索), and respiratory dysfunction or interstitial lung disease (搜索).
Healthcare costs were 7.61-fold higher in patients with iMCD compared to controls, reflecting the substantial economic impact of this rare disorder. "The BURDEN-iMCD findings are consistent among patients with idiopathic multicentric Castleman disease (搜索), with increased morbidity, including organ failure, multisystem dysfunction and thrombotic events, compared to matched controls," Dr. Ohgami noted.
Pediatric Disease Severity and Treatment Response
The largest pediatric iMCD analysis to date, based on the ACCELERATE iMCD natural history registry, compared 30 children (under 19 years at symptom onset) with 96 adults. Children demonstrated more severe disease presentation, evidenced by higher CHA (C-reactive protein, hemoglobin, and albumin) scores at diagnosis, worse anemia (搜索), higher rates of organomegaly, and increased fluid retention.
The severe TAFRO (搜索) subtype of iMCD (thrombocytopenia, anasarca, fever, renal dysfunction (搜索) and/or reticulin fibrosis, and organomegaly) occurred more frequently in children compared to adults. Despite the increased severity, children and adults showed similar response rates to siltuximab treatment, with no new safety concerns identified in the pediatric population.
Comprehensive Subtype Analysis
A 20-year retrospective analysis of 217 patients with CD at the Mayo Clinic Health System between January 2004 and August 2024 provided new insights into disease subtypes. The study characterized the newly described oligocentric CD (OligoCD) subtype, defined as involvement of at least two adjacent lymph node regions, and the idiopathic plasmacytic lymphadenopathy (IPL) subtype of iMCD.
Results suggest that OligoCD falls between unicentric CD and iMCD in terms of severity based on two-year event-free survival rates. One-year event-free survival results reconfirmed TAFRO (搜索) as the most aggressive iMCD subtype, followed by iMCD not otherwise specified and IPL.
Clinical Implications
"Recordati Rare Diseases is at the forefront of enhancing understanding of rare hematologic disorders, as exemplified by our continued support of research in Castleman disease (搜索)," said Alessandro Albuquerque, MD, PhD, Chief Medical Officer and Vice President of Medical Affairs and Clinical Development at Recordati. "We hope these data lead to more timely diagnosis and treatment for people living with this devastating disease."
The research underscores the critical need for earlier recognition and optimized disease management to mitigate the clinical and economic burden of iMCD. Idiopathic multicentric Castleman disease (搜索) is a rare cytokine-driven disorder that may be life-threatening and affects people of any age, with symptoms often resembling malignant lymphoma, autoimmune, or infectious diseases, making diagnosis challenging.
Some patients with iMCD have elevated levels of interleukin 6 (IL-6), a cytokine that plays a central pathological role in the disease and may explain symptoms such as swollen lymph nodes, fever, unexplained weight loss, and night sweats. The current standard treatment, siltuximab (SYLVANT), is approved for multicentric Castleman disease (搜索) in patients without HIV and HHV-8 infection, though it is not approved for pediatric use.