CHARLOTTE, N.C.—Immune checkpoint inhibitors have become an important part of the armamentarium in the treatment of advanced malignancies, but their use is associated with hepatotoxicity. A recent study has identified the risk factors most strongly associated with this adverse event.
To determine the predictors of immune checkpoint inhibitor (ICPI)-induced hepatotoxicity, researchers from Cleveland Clinic mined the IBM Explorys database—which includes electronic health record data from 26 large health systems—looking for patients who developed hepatotoxicity after treatment with one or more of the following ICPIs: atezolizumab (Tecentriq, Genentech), durvalumab (Imfinzi, AstraZeneca), ipilimumab (Yervoy, Bristol Myers Squibb), nivolumab (Opdivo, Bristol Myers Squibb) and pembrolizumab (Keytruda, Merck).
They excluded patients with alcoholism, other drug-induced injury, viral hepatitis or biliary disease, evaluating risk factors including the use of combination ICPIs, concomitant use of cytochrome P450 CYP2E1–enhancing medications, smoking, malnutrition, chronic kidney disease (CKD), metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). “We looked at the elderly population too,” said Osama Hamid, MD, MRCPI, a clinical associate in the Department of Hospital Medicine at Cleveland Clinic in Cleveland, who presented the study at the 2022 meeting of the American College of Gastroenterology (poster C0524).
Of the 69 million patients in the database, Dr. Hamid and his co-investigators identified 21,060 who received ICPIs, 1,780 (8.4%) of whom had ICPI-induced hepatotoxicity. The risk factors most strongly associated with ICPI-induced hepatotoxicity were NAFLD and combination ICPIs, followed by malnutrition and metabolic syndrome.
“It is worth noting that ICPI-induced hepatotoxicity was also significantly associated with CKD, smoking [and] concomitant cytochrome P450 inducers,” Dr. Hamid said. Age was also associated with ICPI-induced hepatotoxicity. In patients who developed ICPI-induced hepatotoxicity, 64.6% were 65 years of age and older, and 35.4% were 18 to 65 years of age.
The main limitation of the study was the researchers couldn’t tell how severe the hepatotoxicity was in those who developed it.
“But the take-home message is that when we start patients on ICPIs, it is very important to keep those factors at the back of our mind if they do develop hepatotoxicity down the line,” Dr. Hamid said.
Mark Russo, MD, MPH, the chief of the Division of Hepatology and a clinical professor of medicine at Atrium Health Transplant and Liver Center, in Charlotte, N.C., commented that Dr. Hamid’s research provides important information on risk factors of hepatotoxicity from ICPIs. “As ICPIs are increasingly used in regimens to treat patients with malignancies, gastroenterologists and hepatologists are likely to encounter consults for elevated liver tests from these agents,” said Dr. Russo, who was not involved in the research. “This study suggests patients with certain comorbidities, such as NAFLD or chronic kidney disease, are at increased risk and may warrant closer surveillance for ICPI-related hepatotoxicity.”
—Monica J. Smith
Drs. Hamid and Russo reported no relevant financial disclosures.
This article is from the February 2023 print issue.