Acute interstitial nephritis (AIN) following immune checkpoint inhibitor (ICI) therapy in metastatic RCC (mRCC) as a potential predictor of response.

Abstract

674 Background: ICIs such as nivolumab (N) have improved outcomes in mRCC patients (pts), but are also associated with immune-related adverse events. As has been shown in melanoma, we hypothesized that pts experiencing an autoimmune reaction directed against the tissue of origin may be more likely to benefit from ICI. Specifically, we evaluated whether pts with nivolumab-induced AIN (N-AIN) exhibited improved outcomes. Methods: We identified all patients with mRCC at UT Southwestern Medical Center from 2014 - 2018 who received at least one dose of N. We extracted creatinine (Cr) values over the entirety of each pt's N treatment course from the electronic medical record. Pts with a 1.5 fold Cr increase over baseline were investigated. The diagnosis of N-AIN was made by biopsy or by clinical criteria (timing of kidney injury, laboratory analysis, and exclusion of other causes). Results: We identified 177 mRCC pts who received at least one dose of N, 36 of whom had at least a 1.5 fold increase in Cr over baseline while on treatment. Of those, two had biopsy-proven AIN and one was clinically diagnosed, resulting in an incidence of 1.7%. Two received N monotherapy after first line, and the third in combination with ipilimumab as initial therapy. The earliest case of N-AIN occurred 1.5 months from N onset, and the others were diagnosed at 11 and 12 months. Of the 3 pts, one had a partial response lasting 2 years, and the other two had a complete response which is ongoing in both pts with over 2 years of follow up. In all 3 cases, N-AIN was treated with cessation of N and prednisone with a return to baseline kidney function. None required dialysis. Conclusions: AIN is a rare event with N, but it may portend a higher likelihood of response. One possible explanation is antigenic crossover between normal renal tubular cells and mRCC, resulting in a robust immune response.