Acute interstitial nephritis linked to immunotherapy response in kidney cancer

November 6, 2020
Jason M. Broderick

Among a small group of patients with metastatic renal cell carcinoma who developed acute interstitial nephritis while on immune checkpoint therapy, 100% had a durable response to treatment.

Immune-related acute interstitial nephritis (irAIN) was associated with a positive response to immune checkpoint inhibitor therapy in patients with renal cell carcinoma (RCC), according to findings from a retrospective analysis published in the Journal for ImmunoTherapy of Cancer.1,2

Among a small group of patients with metastatic RCC who received at least 1 dose of an immune checkpoint inhibitor and developed irAIN, 100% responded to the treatment and had at least partial recovery of renal function.

“For 100% of patients to respond is quite significant,” Roy Elias, MD, assistant instructor of internal medicine at UT Southwestern Medical Center (UTSW) and co-first author of the study, stated in a press release. “If a patient develops AIN, it is a sign that the treatment may be working.”

The researchers launched this study based on the observation that in other cancers, such as melanoma, a response to immune checkpoint therapy may be more likely among patients who have an autoimmune reaction directed against the tumor tissue of origin.

The researchers used the Kidney Cancer Explorer database to identify patients with mRCC who were treated with at least 1 dose of an immune checkpoint inhibitor at (UTSW) between 2014 and 2018.

Overall, there were 177 patients with mRCC who had been administered at least 1 dose of an immune checkpoint inhibitor. The researchers narrowed this group down to 36 patients who had at least a 1.5-fold increase in their creatine level between baseline and the entirety of their immunotherapy treatment course. In this subgroup, 4 patients had irAIN.

Two of the 4 patients with irAIN received frontline treatment with nivolumab (Opdivo) plus ipilimumab (Yervoy) and the other 2 had received second-line nivolumab. The time between treatment initiation and the onset of irAIN ranged between 1.5 months and 1 year.

After having a deep response to immune checkpoint therapy, all 4 patients stopped receiving their treatment with at least partial recovery of renal function. Three of the patients had received systemic steroids.

In the conclusion of their paper, the author wrote that antigenic overlap between normal renal tubular cells and tumor cells was 1 potential explanation for the association between irAIN and response.

“All cancer cells start out as normal cells,” James Brugarolas, MD, PhD, professor of internal medicine and director of the Kidney Cancer Program at UTSW. “Even after turning malignant, they retain some of their original traits. Thus, an attack against the tissue of origin may signal a higher chance that the immune system will also recognize and attack the cancer.”

Nivolumab and ipilimumab are currently approved by the FDA for combination use as a dual checkpoint blockade in the first-line setting for the treatment of patients with intermediate- or poor-risk, advanced RCC. Nivolumab is also approved by the FDA for single-agent use in patients with advanced RCC who have previously received antiangiogenic therapy.

References

1. Immunotherapy Side Effect Could Be A Positive Sign For Kidney Cancer Patients. UT Southwestern Medical Center. Published November 2, 2020. https://bit.ly/2TWAzSz. Accessed November 5, 2020.

2. Patel V, Elias R, Formella J, et al. Acute interstitial nephritis, a potential predictor of response to immune checkpoint inhibitors in renal cell carcinoma. J Immunother Cancer. 2020;8(2):e001198. doi: 10.1136/jitc-2020-001198.

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