Infliximab for Grade III or IV Immune Checkpoint Inhibitor Nephritis Clinical and Translational Evidence.

Introduction: Acute interstitial nephritis (AIN) is a common presentation of immune checkpoint inhibitor (ICI) toxicity. Increased tumor necrosis factor (TNF)-α expression has been observed in ICI-induced AIN (ICI-AIN). In this study, we compared treatment with glucocorticoids plus infliximab to glucocorticoids only in stage III or IV ICI-AIN. We conducted retrospective NanoString analysis of ICI-exposed kidney samples to identify associated gene signatures and possible association with TNF-α expression. Methods: We reviewed the records of patients who received ICI, developed acute kidney injury (AKI), and underwent kidney biopsy at MD Anderson Cancer Center from January 2022 to October 2024. Fifty-five patients had AIN and stage III or IV AKI. 27 received steroids only and 28 received steroids plus infliximab. Time to renal response (TTR), duration of renal response (DORR), and cancer progression-free survival (PFS) were estimated using the Kaplan-Meier method. The log-rank test assessed survival differences between groups. Cox proportional hazards analyses were conducted on TTR and DORR, with treatment as a time-dependent covariate for TTR. Using NanoString technology, inflammatory gene signatures were evaluated in 86 kidney samples, of which 48 were ICI-exposed. Results: No baseline differences were observed between groups. TTR was significantly improved in patients exposed to infliximab within 30 days of starting steroids compared with steroid-only. DORR was longer in infliximab group in univariate but not multivariate analysis, and no PFS difference was observed. In NanoString analysis, immune expression was higher in drug- and ICI-AIN compared with controls. Elevated TNF-α expression in drug- and ICI-AIN correlated with renal response. Conclusion: Infliximab use may offer a therapeutic advantage over steroids alone in stage III or IV ICI-AIN.