Study identifies biomarkers predictive of response to immunotherapy in patients with kidney cancer

Biomarkers derived from hematoxylin and eosin-stained (H&E) pathology slides have been found to be predictive of response to anti-PD-1 therapy in patients with metastatic clear cell renal cell carcinoma (RCC), according to research conducted at the Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland.^1,2

Patients with all 3 factors (a TIL^plus score of 1, a necrosis score of 0, and a PBRM1 mutation) had the greatest overall survival at 5 years.

The results, published in Cell Reports Medicine, point to an accessible way to predict outcomes for immunotherapy in patients with RCC, explained study author Julie Stein Deutsch, MD, in a news release on the findings.² “There are many studies investigating biomarkers for response to immunotherapy using advanced technologies that require expensive machines and experienced technicians. The ability to use information from an H&E slide, pretreatment, to predict overall survival of patients receiving this therapy is extremely powerful and is something that can be used in resource-poor settings as well,” said Deutsch, a clinical fellow in dermatopathology at the Johns Hopkins University School of Medicine.

For the study, H&E slides from 136 metastatic tumor samples were examined from patients with RCC. Among all samples, 63 pre-treatment biopsies were obtained from patients who received nivolumab (Opdivo) as either first-line or later-line RCC treatment, 58 from patients receiving later-line nivolumab or everolimus (Afinitor), and 15 from treatment-naïve patients who received nivolumab plus ipilimumab (Yervoy).

The investigators found that information from the H&E slides in combination with one another could serve as potential biomarkers in predicting patients’ response to treatment. These factors include the number of immune cells in and around kidney tumors, the amount of dead cancer tissue, and the mutations of PBRM1, a tumor suppressor gene.

Among all patients that received immunotherapy, patients who had specimens with a tumor-infiltrating immune cell score (TIL^plus) of 1 were shown to have overall survival of 47.9 months compared with 16 months in patients with a TIL^plus score of 0. Median progression free-survival was also higher among patients with a TIL^plus score of 1, which was 7.5 months, compared with 2.7 months in the group with a TIL^plus score of 0. These findings were specific to patients receiving immunotherapy.

Further, patients who had tumors with necrosis spanning greater than 10% surface area were found to have a lower overall survival compared with patients who had the same TIL^plus score but less necrosis. This finding was again specific to patients receiving immunotherapy.

Mutations in PBRM1 were also found to be associated with overall survival (P =.02).

The 3 biomarkers were then looked at in combination with one another, and the investigators found that patients with all 3 factors (a TIL^plus score of 1, a necrosis score of 0, and a PBRM1 mutation) had the greatest overall survival at 5 years. Conversely, patients with only 1 of the biomarkers had the worst overall survival among all patients.

References

1. Deutsch JS, Lipson EJ, Danilova L, et al. Combinatorial biomarker for predicting outcomes to anti-PD-1 therapy in patients with metastatic clear cell renal cell carcinoma. Cell Reports Medicine. Published online February 21, 2023. Accessed April 6, 2023. doi:10.1016/j.xcrm.2023.100947.

2. Researchers Id biomarkers of response to immunotherapy for kidney cancer. News release. Johns Hopkins Medicine. April 6, 2023. Accessed April 6, 2023. https://www.newswise.com/articles/researchers-id-biomarkers-of-response-to-immunotherapy-for-kidney-cancer?sc=mwhr&xy=10016681