Angela M. Leung
Patients treated with immune checkpoint inhibitors, including CTLA-4 and PD-1 inhibitors, are at an increased risk for developing endocrine immune-related adverse events, particularly thyroid dysfunction, according to research reported in Clinical Endocrinology.
“This study highlights the increasing recognition that immunotherapies used in the management for a variety of cancers may impact the endocrine system,” Angela M. Leung, MD, MSc, assistant professor of medicine in the division of endocrinology, diabetes and metabolism at the UCLA David Geffen School of Medicine, told Endocrine Today. “Specifically, use of CTLA-4 and PD-1 inhibitors, through downregulation of autoreactive T cells, is associated with an increase of several immune-activated types of endocrine dysfunction. We confirm in this study that the majority of endocrine dysfunction effects are thyroid-related, likely through activation of thyroid autoantibodies.”
In a retrospective review, Leung, Natalie M. Villa, a doctoral student at the UCLA David Geffen School of Medicine, and colleagues analyzed data from 388 patients prescribed ipilimumab (Yervoy, Bristol-Myers Squibb), nivolumab (Opdivo, Bristol-Myers Squibb) or pembrolizumab (Keytruda, Merck) between 2009 and 2016 (mean age, 63 years; 56.4% men; 71.7% white). Researchers assessed laboratory and radiographic results to evaluate incidence of primary thyroid dysfunction, hypopituitarism, primary adrenalitis and pancreatitis after the use of immunomodulatory therapies.
Within the cohort, researchers observed 50 endocrine immune-related adverse events (12.9%). The mean time to event was 17.85 days.
The most common immune-related adverse event was thyroid dysfunction, observed in 43 patients (11.1%) with a mean time to event of 8.88 days. Ten patients developed overt hypothyroidism, 21 patients developed subclinical hypothyroidism, nine patients experienced overt hyperthyroidism and three patients developed subclinical hyperthyroidism.
Seven patients (1.8%) had evidence of hypopituitarism, with a mean time to event of 16.71 days. There were no observed cases of primary pancreatic or adrenal immune-related adverse events, according to researchers.
“Given the potentially permanent nature of some of the endocrine dysfunction problems that may follow use of these treatments, monitoring for biochemical endocrine abnormalities should be routinely done before, during and following therapy,” Leung said. “This is not currently being done systematically, and further research should focus on the cost-benefit ratio of routinely screening for these endocrine problems and at what interval the screening should be done.” – by Regina Schaffer
For more information:
Angela M. Leung, MD, MSc, can be reached at the UCLA David Geffen School of Medicine, Division of Endocrinology, Diabetes and Metabolism, 10833 Le Conte Ave., Los Angeles, CA 90095; email: firstname.lastname@example.org.
Disclosures: Leung and Villa report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.