Introduction
Our patient first presented in 2017 with multiple sites of lymphadenopathy (right submandibular, right cervical, pericardiac, periportal, paraaortic) and small volume liver lesions. Biopsy showed adenocarcinoma, CK7+ (diffuse) CK20+ (patchy), TTF-1 -. Pan-endoscopies were negative. Impression was that of CUP, possibly head and neck or pancreatobiliary in origin. He had a partial response (PR) after #6 of Paclitaxel and Carboplatin but developed paraesthesia. After a break of 4m, he developed a new liver lesion. He progressed after #3 of TS-1, and switched to Gemcitabine on which he had PR at 4m before disease progression (PD) at 6m, then PD after 2m of Capecitabine and Irinotecan. His biopsy was molecularly profiled and with a TMB of 15 mut/Mb, he was started on combination PD-1 and CTLA-4 ICB.
Case presentation
He had a PR and tolerated treatment well aside from G1 xerostomia, but developed G2 hypophysitis requiring replacement steroids 3m after ICB initiation. 8 months after ICB initiation, he developed G2 acute kidney injury (AKI) with peak serum creatinine (sCr) of 299mmol/L (baseline sCr100 mmol/L). Urinalysis showed pyuria (13 WBC) without hematuria or proteinuria. Kidney biopsy revealed substantial interstitial inflammation with a predominantly CD8+ infiltrate and scattered plasma cells, and acute tubular injury, consistent with ICB- induced AIN. Oral prednisolone (PRL) was initiated at 60mg OD (1mg/kg) with improvement to G1 AKI (sCr 133mmol/L) by week 2. PRL taper resulted in a relapse (sCr 167 umol/L) at week 3, requiring maintenance of high dose PRL. Mycophenolate mofetil (MMF) was initiated at week 6 in view of suboptimal response despite high dose PRL.
Discussion
AIN is the most common renal irAE. Corticosteroids remain 1st-line therapy with most achieving good response. Suboptimal response or relapse during steroid taper warrants consideration of 2nd line immunosuppression although the optimal agent is unknown. Immunohistopathology has been proposed to individualise an approach and the predominant T-cell infiltrate in our patient lends mechanistic support to the use of MMF as a 2nd-line agent.