Blood Test Could Detect Adverse Immunotherapy Effects

Immune checkpoint inhibitors have transformed cancer treatment, but they can also trigger serious immune-related adverse events that damage healthy organs and may become life-threatening if not detected early. Currently, clinicians rely largely on symptoms to diagnose these toxicities, which often appear only after significant injury has occurred. Now, a new study suggests that a simple blood test can reveal hidden, multi-organ tissue damage days to months before immune-related side effects are clinically diagnosed.

In the study led by investigators at the Johns Hopkins Kimmel Cancer Center (Baltimore, MD, USA), the team explored whether circulating cell-free DNA in blood could serve as a noninvasive marker of tissue injury caused by immune checkpoint inhibitor therapy. The approach leverages the fact that different organs release DNA fragments with unique methylation patterns when cells are damaged. By analyzing these epigenetic signatures, the test can identify which organs are affected and quantify the extent of injury without requiring biopsies or imaging.

The research focused on patients receiving immune checkpoint inhibitors, drugs that stimulate the immune system to attack tumors but can also cause immune-mediated inflammation in organs such as the lungs, gastrointestinal tract, liver, and skin. Because immune-related adverse events can involve multiple organs simultaneously, a systemic monitoring tool could offer a major clinical advantage. Blood samples were collected before treatment and again between four and eight weeks after therapy initiation, allowing researchers to track tissue damage over time and compare patients who developed immune-related toxicities with those who did not.

The study included 14 patients with solid tumors, six of whom developed immune-related adverse events. All six showed evidence of multiorgan tissue damage based on elevated levels of tissue-specific cell-free DNA, with approximately sixfold higher concentrations than patients without adverse events. In three patients, signs of tissue injury appeared four to 236 days before clinical symptoms led to an immune-related adverse event diagnosis. None of the eight patients without documented toxicities showed evidence of multiorgan damage.

The findings, reported in a letter to the editor in The New England Journal of Medicine, suggest that immune-related toxicities may be more widespread than clinical symptoms alone reveal. A blood-based cell-free DNA test could help clinicians identify patients at risk earlier, monitor ongoing organ injury, and intervene before severe complications develop. Researchers note that larger clinical trials are needed to validate the approach and clarify how different patterns of tissue damage relate to treatment decisions. If confirmed, this strategy could become a powerful tool for improving the safety of cancer immunotherapy.

Related Links:
Johns Hopkins Kimmel Cancer Center