Acute interstitial nephritis may predict response to immune checkpoint inhibitors in renal cell carcinoma

November 2020 Science Tobias Rawson

Following the apparent association between immune-related adverse events and the malignant tissue of origin with improved clinical outcomes, a recent study has concluded that the development of immune-related interstitial nephritis in patients with renal cell carcinoma, in response to the administration of immune checkpoint inhibitor (ICI) therapy, may be a predictor of depth of response, and therefore, clinical outcome.

Deep level of response

Using the Kidney Cancer Explorer, a data-registry at the University of Texas Southwestern Medical Centre for renal carcinoma patients, this study identified 36 patients who had metastatic renal cell carcinoma, a creatinine concentration over 1.5-fold above baseline, and who had be given at least one dose of ICI therapy. Of the 36 patients identified, 4 patients had acute interstitial nephritis diagnosed either clinically or through biopsy. These patients all developed interstitial nephritis following the administration of ICI therapy, with all patients demonstrating at least partial recovery of renal function, following ICI cessation. Despite each of these patients having an individual course of disease, all 4 patients exhibited a deep level of response, with 2 patients demonstrating long term disease control, even after the cessation of systemic therapy. Of particular note, is the fact that these 4 patients presented with pathological findings associated with poor prognosis, such as bone and hepatic metastasis, as well as diffuse peritoneal carcinomatosis.

Antigenic overlap

The positive clinical outcome of these patients supports the notion of antigenic overlap, in which the development of immune-related adverse events, specific to the malignant tissue of origin is due to antigenic spread following a successful antitumour response, resulting in the immune recognition of epitopes on healthy cells that resemble those found previously on malignant cells.

Renal cell carcinoma affects approximately 10.9/100,000 men and 5.3/100,000 women in Belgium every year, with a 5-year survival rate of 76.7% and 78.6%, respectively. Despite ICI therapy not being generally curative, this new, biopharmalogical approach does represent an intervention that can offer eligible patients precious time, with some benefitting, evidently, from a sustained depth of response.