First new subtype of Castleman disease discovered in 45 years

PHILADELPHIA— A newly identified subtype of Castleman disease will help diagnose and properly treat thousands of patients who have been caught between existing classification systems, marking the first major discovery of its kind in 45 years. "Oligocentric Castleman Disease" (OligoCD) has been found to be a distinct clinical entity, different from the two previously identified classifications of Castleman Disease. The findings, which redefine the understanding of this rare immune disorder that affects an estimated 4,300 to 5,200 Americans, are published this week in Blood Advances by researchers from the Perelman School of Medicine at the University of Pennsylvania.

“This discovery is a game-changer for Castleman disease patients,” said David Fajgenbaum, MD, an associate professor of Translational Medicine and Human Genetics at Penn and co-founder of the Castleman Disease Collaborative Network (CDCN). “For decades, patients with OligoCD have been falling through the cracks, classified as having a different type of Castleman Disease and being subjected to potentially over-aggressive treatments such as chemotherapy that come with very uncomfortable side effects.  Now we can match these patients—about 15 percent of all Castleman cases—with the right treatments for their specific condition.”

Castleman disease (CD), first described in 1956 by Dr. Benjamin Castleman, encompasses a spectrum of conditions characterized by abnormal lymph node growth and a range of symptoms from mild to life-threatening. Historically, CD has been divided into UCD, involving a single lymph node region with milder symptoms, and iMCD, marked by widespread lymphadenopathy and severe, cytokine-driven inflammation. However, some patients’ experiences with CD don’t fit these two types, complicating diagnosis and care.

Using the ACCELERATE registry—which combines medical data from hundreds of patients with CD so that researchers and physicians can better understand and treat CD—the research team ofclinicians and hematopathologists analyzed 179 patients.

The study found that OligoCD patients exhibit fewer and less severe symptoms than those with iMCD, suggesting that surgical removal of affected lymph nodes—effective for the milder UCD—may be more appropriate than the intense treatments used for iMCD. Therapies for iMCD include IL-6 inhibitors used for serious rheumatoid arthritis, immunosuppressants used for autoimmune disease and transplants, and chemotherapies. However, the team emphasizes the need for further research to refine treatment guidelines and a further understanding of how OligoCD develops, with ACCELERATE poised to provide ongoing insights.

“ACCELERATE has consistently proven to be an invaluable tool in unlocking the mysteries of Castleman disease,” said Josh Brandstadter, MD, PhD, director of clinical research at Penn’s Center for Cytokine Storm Treatment & Laboratory. “Without the robust data from patients around the world, we would not have been able to redefine the CD spectrum with such clarity.”

The Penn Clinical and Research teams also worked with several patients from the Castleman Disease Collaborative Network (CDCN) who shared their experiences, which helped  identify the gaps in existing classifications and inspired the push to define OligoCD as a new subtype.

Penny Deremer is a member of the CDCN and a Penn Medicine patient with OligoCD.

“I am so thankful to finally have a name for what I and so many other patients have been going through,” she said.

Editor’s Note: The ACCELERATE natural history registry has received funding from Janssen Pharmaceuticals (2016 — 2018), EUSA Pharma, LLC (US), which has merged with Recordati Rare Diseases Inc. (2018 — 2022), and the U.S. Food & Drug Administration (R01FD007632).

Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System (UPHS) and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.

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