Infliximab for Immune Checkpoint Inhibitor-Associated Acute Interstitial Nephritis: A Biomarker-Guided Approach

Background: Immune checkpoint inhibitor associated acute interstitial nephritis (ICI-AIN) occurs in 3-5% of patients receiving ICI therapy, and is typically steroid responsive. A minority of cases are steroid dependent. We review the outcomes of patients with steroid-dependent ICI-AIN treated with Infliximab at our center, as well as the relationship between several non-invasive biomarkers and response to therapy. Methods: We describe 3 cases of biopsy-proven ICI-AIN for which Infliximab was used as a steroid sparing agent. We followed several biomarkers including: urine CXCL9, urine TNF-α, urine RBP -- all normalized to creatinine, serum IL2r and CRP at varying time points in the disease course. Serum TNF-α was measured to monitor Infliximab response. Results: Clinical characteristics are described in Table 1. Figure 1 depicts biomarker trends over time as a function of therapy. All 3 patients had relapse of their ICI-AIN with prednisone taper ≤ 20 mg. Post 1 infliximab infusion, patient 2 was tapered off steroids. Patient 1 and 3 remained on Prednisone 10 mg post 2 doses of Infliximab for other indications. Serum TNF-α was suppressed with Infliximab in all cases. All patients had elevated urine TNF-α/Cr, CXCL9/Cr, RBP/Cr, and serum IL2r at initial diagnosis which decreased with therapy. When measured around the time of ICI-AIN relapse, urine RBP/Cr, CRP, urine TNF-α/Cr, and urine CXCL9/Cr all rose. Conclusion: In all cases, Infliximab facilitated steroid taper and biomarker trends helped determine the number of Infliximab doses before significant rises in creatinine occurred. Controlled studies are needed to clinically validate these biomarkers for ICI AIN diagnosis and relapse.Table 1 - Patient 1 Patient 2 Patient 3 Age (y) and Sex 63, Male 90, Female 74, Male Cancer Type and ICI Therapy Renal Cell Carcinoma, on Ipilimumab and Nivolumab Breast Cancer, on Pembrolizumab Non-Small Cell Lung Cancer, on Pembrolizumab Preceding Immune Related Adverse Events Pneumonitis, Hypophysitis Myocarditis Myocarditis ICI Re-Challenge Yes, on Prednisone 10 mg daily No, cancer remains in remission Yes, on Prednisone 10 mg daily