Study details incidence & timing of immunotherapy-related fatalities

September 13, 2018

Vanderbilt-Ingram Cancer Center researchers have answered questions about the incidence and timing of rare but sometimes fatal reactions to the most widely prescribed class of immunotherapies.

Their research, which appeared Sept. 13 in JAMA Oncology, is the largest evaluation of fatal immune checkpoint inhibitor toxicities published to date. They determined that although these severe events can happen, the risks are "within or well below" fatality rates for more common cancer treatments, including chemotherapy, stem cell transplants and complex cancer surgeries.

When fatal reactions did occur, they tended to happen early after starting treatment, on average 15-40 days, depending upon the type of immune checkpoint inhibitor. Their study further characterized the fatal toxicities and timing of reaction by type of cancer and specific drug.

"These drugs are quite transformative," said Douglas Johnson, MD, MSCI, senior author of the article. "The benefits outweigh the risks, but patients and doctors should be aware of their toxicities. These side effects can be quite severe, and they are something that we really need to pay attention to."

The team sorted through more than 16 million adverse drug reaction reports in a World Health Organization (WHO) database searching for those related to immune checkpoint inhibitors. They also reviewed the records from seven academic centers, including Vanderbilt, that have been at the forefront of immunotherapy research. Additionally, they conducted a meta-analysis of published trials for the drugs.

Checkpoint inhibitors unleash the immune system to attack cancer, but they may also spur an attack on organs, including the heart, lungs, liver and colon. Steroids are prescribed to relieve the resulting inflammation: myocarditis, pneumonitis, hepatitis and colitis, and are usually extremely effective. Timely treatment with steroids is crucial, Johnson said.

"Some of the patients who died had a long delay before they received steroids," Johnson said. "In some cases, the patient didn't call in to report their symptoms or experienced a very unusual presentation that was difficult to diagnose."

The data also showed that older patients were more prone to experience fatal toxicities, although the occurrence was still rare.

"We don't necessarily think that older patients have more side effects, but when they do have toxicities, they can potentially have more complications," Johnson said.

The team found 613 fatal immune checkpoint inhibitor toxicities within the more than 16 million reports in the WHO pharmacovigilance database (Vigilyze) from 2009 to 2018. Myocarditis (inflammation of the heart) had the highest fatality rate, as nearly 40 percent of patients with this side effect died.

The review of records from the seven academic centers revealed a 0.6 percent fatality rate. The meta-analysis of data from 112 clinical trials showed a fatality death rate ranging from 0.36 percent to 1.23 percent, depending upon the specific type of immune checkpoint inhibitor.

The study notes that this range is "dramatically lower than the near 100 percent fatality rate for metastatic solid tumors." The U.S. Food and Drug Administration has at this point in time approved immune checkpoint inhibitors for 13 different types of metastatic cancers.

"We have clinics full of patients now who received these treatments who are alive today because they responded to these treatments," Johnson said.
-end-
The study was supported by the National Institutes of Health/National Cancer Institute, The Cancer ITMO of the French National Alliance for Life and Health Sciences, the James C. Bradford Jr. Melanoma Fund and the Melanoma Research Foundation.

Vanderbilt University Medical Center

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.