HMS Study Sheds Light on Link Between Heart Condition and Cancer Treatment

A new study out of Harvard Medical School is opening the door for cancer patients with a rare but dangerous heart condition to continue immunotherapy treatment for the first time.

HMS researchers from Massachusetts General Hospital and the Broad Institute of MIT and Harvard analyzed tissue from 28 patients in the study, published in Nature on Nov. 6.

“We wanted to figure out if the biology that is driving this heart inflammation is different from the biology tied to the tumor,” said Alexandra-Chloé Villani, an assistant professor of medicine at HMS and co-author of the study.

After more than six years, researchers have discovered that the answer is yes.

Their research shows that myocarditis — a form of heart inflammation sometimes triggered by immunotherapy — is separate from the treatment’s desired immune response against tumors. This means that patients may be able to continue immunotherapy while receiving targeted treatments to address the inflammation.

According to Kerry L. Reynolds, HMS assistant professor and co-author of the study, myocarditis is rare but deadly.

“We treat 1,000 new patients here at Mass General with immunotherapy a year, and only 1 percent get myocarditis, literally about 10 patients a year,” she said. “The problem with this condition is that it is highly morbid.”

She added that 30 percent of patients with myocarditis can experience severe heart issues — including cardiac arrest or even death. Cancer patients who develop myocarditis are often taken off of life-saving immunotherapy treatment to prevent these symptoms.

Steven M. Blum, HMS instructor and co-author of the study, said that this new research “gives us some hope that we could potentially treat patients more safely.”

“This was the first study to look in human heart samples, to actually examine the percentages of the cells in the hearts of these patients,” Blum added. “Through some cutting edge technologies, we were able to define some of the cell populations that are associated with this disease.”

Thanks to these innovations, the study identified indicators in patients’ blood that may predict patients’ likelihood of death from myocarditis.

“If you want to think about drug targets to mitigate, to treat myocarditis, you first need to figure out what’s so special in the heart of these patients,” Villani said.

Blum said the study, which was conducted under the Severe Immunotherapy Complications Service and Clinical-Translational Research Effort, included a sample size “significantly larger than anything else that was in the literature.”

“We are very, very grateful to the patients and their families who participated,” Dan A. Zlotoff ’05, co-author and HMS instructor, said. “They were willing to offer their body to science — that is an enormous gift to patients and families that come after them.”

Reynolds said that the study will trigger “a lot more investigation.”

“This is a fundamental, foundational study,” she said.

Reynolds cited an ongoing HMS clinical trial examining a potential pharmaceutical treatment for myocarditis as an example of expansion of the study’s results.

“This is a trial that involves more than 45 sites in the US and Canada,” Zlotoff said. “We’re hoping to build an even larger repository of both tissue and blood samples.”

Blum said that the HMS study is a “progress of science,” and believes it will help “move the field forward” to better understand myocarditis.

“There has never been a better time to be in medicine and science,” Reynolds added. “The discoveries are coming fast and furious, and I really do feel like the next decade will look completely different than the last.”