In addition to serving as clinical director of the Myeloma Center at the University of Arkansas for Medical Sciences (UAMS), Frits van Rhee, M.D., Ph.D., is also regarded as an international expert on Castleman disease, a rare disorder of the lymph nodes and related tissues.
“Because Castleman disease is rare, most physicians don’t know how to treat it, and until recently there was not any systematic approach,” said van Rhee, who also holds the Charles and Clydene Scharlau Chair for Hematologic Malignancies Research at UAMS. Castleman disease affects approximately 5,000 patients across the United States.
Identified by Benjamin Castleman, M.D., in 1954, Castleman disease occurs when an abnormal overgrowth of cells occurs in the lymph system, which serves as the main part of the body’s immune system.
“The average oncologist may only see one patient with Castleman disease in his career,” said van Rhee, who has worked to advance the research and treatment of the rare disease.
Van Rhee previously served as the principal investigator on a worldwide trial with siltuximab (Sylvant), which led to the first FDA-approved treatment for multicentric Castleman disease and the approval of the drug by the European Medicine Agency.
Recent new discoveries were led by researchers at Penn Medicine and the Castleman Disease Collaborative Network, (CDCN) which van Rhee co-founded in 2012 with David Fajgenbaum, M.D., an iMCD patient of van Rhee’s and the study’s senior author. Fajgenbaum, who received his medical degree after being diagnosed with Castleman disease, is an assistant professor of Translational Medicine and Human Genetics, director of the Center for Cytokine Storm Treatment & Laboratory at the Perelman School of Medicine at the University of Pennsylvania and associate director of patient impact at the Penn Orphan Disease Center.
One of these studies revealed a precision medicine test using blood proteins to identify a novel patient subgroup of iMCD patients who are more likely to respond to siltuximab. The study, published by Blood Advances, also found that using Janus kinase (JAK) inhibitors, which are already approved for treating certain cancers and rheumatoid arthritis, are a promising alternative treatment option for patients who do not respond to siltuximab, a monoclonal antibody treatment.
Other studies published by Fajgenbaum and van Rhee in the journals Blood and the Journal of Clinical Investigation found another new target for therapy, m-TOR, for patients who do not respond to siltuximab. The University of Pennsylvania and the University of Arkansas for Medical Sciences are currently conducting a clinical trial with sirolimus, which inhibits m-TOR, for MCD adult patients who are unable to benefit from the anti-IL-6 therapies, which include siltuximab and tocilizumab (Actemra).
Van Rhee has also written a book, Castleman Disease, as part of the Hematology/Oncology Clinics of North America series of clinics review articles published bimonthly by Elsevier Inc. The book, published in early 2018, marked the first time since the disease was identified more than 50 years ago that anyone had written a book exclusively about it. In late 2018, van Rhee was the lead author on a paper that established international guidelines for treating idiopathic MCD. The guidelines were designed to give treating physicians a framework for the diagnosis and treatment of this type of Castleman disease. Most of the recommendations were reached by consensus of an expert panel, which met through coordinated meetings of the CDCN. In late 2016, an international registry for patients with Castleman disease was created to collect patient outcomes to increase the evidence base for selection of future therapies.
Van Rhee also was lead author on a paper published in 2020 that established consensus diagnosis and treatment guidelines for another form of the disease, unicentric Castleman disease (UCD), which affects a single lymph node area. It is the most common type of Castleman disease and can usually be treated with surgery, said van Rhee.