Precision Medicine Test Predicts Patient Response to Treatment

September 07, 2021 - A new study indicated that a precision medicine test using blood proteins can identify patients with idiopathic multicentric Castleman disease (iMCD) and are most likely to respond to treatment.

The international study was the joint undertaking of University of Pennsylvania School of Medicine researchers and the Castleman Disease Collaborative Network (CDCN). Currently, siltuximab is the only Food and Drug Administration (FDA) approved treatment method for Castleman disease.

Prior research suggests that about half of patients do not respond to the monoclonal antibody treatment, siltuximab. For those patients, rapid administration of other treatments is critical to prevent the condition from worsening.

The study also revealed that an existing drug approach, Janus kinase (JAK) inhibitors, which are already approved for treating certain cancers and rheumatoid arthritis, could be an alternative for patients who do not respond to siltuximab.

“This discovery has the potential to improve precision medicine for iMCD — the concept that the right patient is given the right drug at the right time. Knowing which patients are likely to benefit from which drugs is a key piece of this puzzle,” senior study author David Fajgenbaum, MD, MBA, MS, said in a press release.

Fajgenbaum is also an iMCD patient.

Castleman disease is not a single disease but a term that describes a group of inflammatory disorders. In the United States, around 5,000 people are diagnosed each year.

Patients experience a range of symptoms from a single enlarged lymph node with mild flu-like symptoms to enlarged lymph nodes located throughout their body, abnormal blood cell counts, and life-threatening failure of multiple organ systems

The most severe subtype is iMCD, which is similar to autoimmune conditions and cancer and involves a cytokine storm. Around 35 percent of patients diagnosed with iMCD will die within five years.

Studies have indicated that siltuximab can send between one-third and one-half of patients into remission lasting years. However, patients in the intensive care unit and don’t respond to siltuximab have few options and limited time.

The patients typically receive chemotherapy but often relapse, meaning many iMCD patients undergo months without appropriate treatment. According to Fajgenbaum, it took him 11 weeks to be correctly diagnosed.

For the study, researchers examined blood sampled from 88 iMCD patients and measured 1,178 blood proteins in each sample. As a result, the team discovered seven blood proteins that could predict the subgroup of patients who were most likely to respond to siltuximab.

“Had this test been available for me, I would have likely gotten second-line treatment more rapidly, lowering my risk of death while I was waiting to see if first-line treatment would work. But just as importantly, this study also identifies another potential treatment to be included in our arsenal,” Fajgenbaum said.

Previous research has shown that in many cases, the cytokine storm in iMCD is associated with a cytokine, or inflammatory mediator, called interleukin-6 (IL-6), potentially opening new precision medicine treatment options.

The study advanced these finding further and found that another pathway call JAK seems to be a crucial mediator of the cytokine storm, potentially providing relief for patients.

“These aren’t findings that require decades of study before they can benefit patients. These drugs can potentially be used right away to help iMCD patients with no other options because they are already approved by the FDA for other diseases. We are basically searching for and finding solutions that are hiding in plain sight,” said the study’s first author Sheila Pierson, MS.