PHILADELPHIA—An innovative, new, patient-driven natural history registry for the rare and poorly understood immune system disorder Castleman disease (CD) will propel care and research for CD through a collaborative research agreement between Janssen Research & Development, LLC; the Castleman Disease Collaborative Network (CDCN); and the University of Pennsylvania.

David Fajgenbaum, MD, MBA, MSc, an assistant professor of Medicine at the Perelman School of Medicine at the University of Pennsylvania and associate director of patient impact at the Penn Orphan Disease Center, will lead ACCELERATE (Accelerating Castleman Care with an Electronic Longitudinal registry, E-Repository, And Treatment Effectiveness research), an international, observational, web-based registry that combines clinical data and patient-reported data to aid in the understanding of the disease and facilitate further research projects. Rather than needing physicians to enroll patients and enter patient data, ACCELERATE allows CD patients to enroll themselves into the registry and make their electronic and paper-based medical records available for research. Then, Fajgenbaum and his team will extract key data from patients’ medical records—including diagnoses, treatments, and clinical outcomes—into the registry.

Patients can learn more about ACCELERATE and enroll at

This first-of-its-kind model gives patients the power to contribute their personal data and the opportunity to be a part of improving understanding and treatment of their disease.

Fajgenbaum, who has battled the idiopathic multicentric (iMCD) subtype of CD as a patient since 2010, when he was a student in Penn’s Perelman School of Medicine, will serve as the principal investigator for the project.  Fajgenbaum spent over six months hospitalized in critical condition and even received Last Rites in November 2010, but after undergoing several rounds of chemotherapy, he rebounded. Since then, he has dedicated his life to advancing research and treatment of the disease. In 2012, Fajgenbaum co-founded the CDCN, a global network dedicated to accelerating research for CD. The CDCN will provide scientific expertise to ACCELERATE through its 28-member Scientific Advisory Board and will engage patients in the research process.

“As a patient and researcher, I am very hopeful that this study will provide clues about CD and optimal patient care,” Fajgenbaum said. “It has the potential to be transformative for the field and for patients.”

iMCD is one of three subtypes of CD, which involves multiple organ system dysfunction due to uncontrolled immune cell activation for an unknown cause. CD is diagnosed in approximately 6,500 to 7,700 Americans of all ages each year -- about the same incidence as amyotrophic lateral sclerosis (ALS).  About 35 percent of iMCD patients die within five years of diagnosis, which is approximately the same as the average across all forms of cancer. CD has a wide spectrum of symptoms, from mild flu-like symptoms to sepsis-like multiple organ failure.

There is one U.S. Food and Drug Administration-approved treatment for iMCD, siltuximab, which is an anti-Interleukin-6 monoclonal antibody developed by Janssen. The therapy demonstrated reduction in lymph node size and disease symptoms in a large portion of patients in its registrational trial. Still, many questions exist related to iMCD, particularly for those patients who do not respond to siltuximab. Research is urgently needed, Fajgenbaum said.

ACCELERATE’s aims are to elucidate the key clinical and laboratory outcomes related to CD, track real-world treatment use and safety profiles, and build an infrastructure for future translational research.  

The team aims to enroll over 1,000 patients within the first five years. Patients from all over the world are able to register. In Europe and other countries where medical records will be provided by healthcare professionals, ACCELERATE will work with clinical sites and medical institutions to collect patient data. The CDCN is also in the process of developing a biobank to streamline the collection, storage, and processing of blood and tissue samples from the CD community.

Though this is an unprecedented project, it does reflect several important recent trends, Fajgenbaum said.

“More and more patients with rare diseases are taking matters into their own hands to connect patient and physician-researcher communities, generate awareness, and drive scientific efforts. With ACCELERATE, patients power the research,” Fajgenbaum said. “It’s also reflective of the value that comes from collaborations between industry, research foundations, and academia to answer tough questions that could ultimately lead to better clinical care.”

Fajgenbaum and his colleagues have authored several key papers in the literature, including a case report on himself in JAMA Dermatology. His publication in the journal Blood initiated a paradigm shift in the iMCD disease model and classification system. He has also co-authored two recent papers, including a systematic literature review in The Lancet Haematology on iMCD and a commentary on CDCN's  “Collaborative Network" approach, as well as the largest-ever series on the newly-described TAFRO Syndrome subtype of iMCD in the American Journal of Hematology.

Reporting in the March 2016 issue of Lancet Haematology, Fajgenbaum and his co-authors, including Penn’s Vera P. Krymskaya, PhD, present several key findings that have advanced the field’s understanding of the disease. They found that the prevalence of cancer among iMCD patients was three times higher than people without the disease. Also, 88 percent of patients studied had a two-year survival rate, 22 percent died by the time of follow-up (median time of follow-up was 29 months), and 41 percent of patients did not respond to first-line treatment, the team found.

“While studies like this provide much-needed data on this population, I believe ACCELERATE will be the seminal project that helps fill the knowledge gaps and propel research even further,” Fajgenbaum said.  “As a physician–scientist and patient with a deadly disease, I believe a more collaborative, strategic, and focused approach is necessary to accelerating research. We must work together to make every dollar and second count, because patients—like me—are waiting.”

Editor’s note: Fajgenbaum participated in an unpaid capacity at two ad hoc advisory board meetings designed by Janssen Pharmaceuticals to gather stakeholder feedback.  Dr. Fajgenbaum contributed both as a patient and researcher.

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 and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.

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