Background Immune check-point inhibitor (ICI) associated acute interstitial nephritis is a rare side effect of IO and literature on IO re-challenge in these patients remain unknown.

Methods We performed a retrospective review of patients who received IO and developed biopsy-proven or clinically suspected ICI associated AIN between January 2003- September, 2022 at the University of Virginia, Emily Couric Clinical Cancer Center. We analyzed details regarding diagnosis, concomitant medications & comorbidities, baseline patient characteristics, clinical course, management, rates of treatment interruption and re-challenge and subsequent outcome. Complete recovery (CRc) was defined as return of kidney function to baseline; partial recovery (PRc) defined as improvement in serum creatinine but >0.3mg/dL from baseline-< 2 x baseline.

Results A total of 1979 patients receive ICI therapy for various indications. Of these, 4 cases of biopsy proven ( 33%) or 8 (66%) clinically suspected ICI associated AIN were identified. Median age was 69 years (57–86), M:F ratio was 2:1 and 9 (75%) were White. Median BMI was 28 (21–39). Most frequent cancers were NSCLC (42%), RCC (33.3%) and melanoma (16.7%). 20% (n= 2) received combination anti-CTLA4 plus anti- PD1, 50% (n=6) received anti-PD1 alone and 30% (n=4) received chemo-immunotherapy. 25% (n=3) patients were on NSAIDS, 42% (n=5) on PPI concomitantly. Intent of IO was adjuvant in 30% patients and palliative for 70% of patients. Median number of infusions before AIN onset was 9 (3–31), and 58% (n=7) developed AIN within first 5 cycles. 66% (n=8) developed ≥ G3 AKI. 4/12 patient underwent renal biopsy, and 11/12 had nephrology consultation. IO was interrupted in 4 (30%) patients, permanently discontinued in 7 pts (58%). Median duration of IO interruption was 221 days, median duration of steroid use was 4.5 weeks. Rate of CRc and PRc were 66% and 8%, respectively. Additional irAE was seen in 50% of patients (concurrent in 2pts, subsequent in 4 pts). IO was resumed in 30% (n=4) of pts. 3 (25)% patients continued to receive ICI therapy following rechallenge till PD/additional irAE or therapy completion. At the time of AIN onset, best disease response was SD in 5 pts, PR in 3 pts, and PD in 3 pts. Median overall survival was 4.87 years and performance free survival was 1.5 years.

Conclusions Re-challenge of IO after kidney irAE is possible in a proportion of patients and needs careful evaluation on an individual basis.

Acknowledgements We thank the University of Virginia Department of Hematology and Oncology for their assistance in the technical workup in this case.

Ethics Approval This work was reviewed by the University of Virginia Institutional Review Board and was approved according to protocol # HSR 24436.