Fatal reactions to immunotherapies are rare, but have diverse causes

Carlotta Jarach

The most commonly prescribed class of immunotherapies (called ICIs, immune checkpoint inhibitors) are not free from fulminant and fatal toxic side effects; the researchers of the Vanderbilt-Ingram Cancer Center recently evaluated their toxicities, publishing the results in JAMA Oncology.The investigation about fatal immune checkpoint inhibitors concluded that, although such events do happen, the risks are “within or well below” fatality rates for more common cancer treatments, including chemotherapy.

From JAMA Oncology:  https://jamanetwork.com/journals/jamaoncology/fullarticle/2701721

The team examined more than 16 million adverse drug reaction reports from 2009 to 2018 in the WHO pharmacovigilance database (Vigilyze), finding 613 fatal immune checkpoint inhibitor toxicities. They also assessed the records from seven academic centers, including Vanderbilt itself, that are the leading edge for immunotherapy research. Also, they conducted a meta-analysis of published trials for the drugs.

Checkpoint inhibitors affect the immune system, assailing the cancer, but doing that they may also attack organs, mainly the heart, lungs, liver and colon. Steroids are prescribed to relieve the resulting inflammation: myocarditis, pneumonitis, hepatitis and colitis. Those inflammation are responsible for the deaths.

According to the results, myocarditis had the highest fatality rate, since almost 40 percent of those people who incur in it had died, whereas endocrine events and colitis had only 2% to 5% reported fatalities. When fatal reactions did occur, they happen on average 15-40 days after starting treatment, depending on the immune checkpoint inhibitor used. “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 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 on the type of immune checkpoint inhibitor. The study noted that this range is “dramatically lower than the near 100 percent fatality rate for metastatic solid tumors”. “We have clinics full of patients now who received these treatments who are alive today because they responded to these treatments,” Johnson said.

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