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Abstract: SA-PO113

A Pathological Immunological Approach in Evaluating Immune Checkpoint Inhibitor-Induced Nephritis

Session Information

Category: Onconephrology

  • 1600 Onconephrology

Authors

  • Abudayyeh, Ala, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
  • Suo, Liye, The University of Texas Health Science Center at Houston John P and Katherine G McGovern Medical School, Houston, Texas, United States
  • Mamlouk, Omar, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
  • Abdel-Wahab, Noha, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
  • Lin, Yan Heather, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
  • Page, Valda D., The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
  • Lin, Jamie S., The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
  • Tchakarov, Amanda, The University of Texas Health Science Center at Houston John P and Katherine G McGovern Medical School, Houston, Texas, United States
Background

Immune related adverse events (irAEs) are a management challenge with an associated increased morbidity and mortality. The most common renal toxicity is acute interstitial nephritis (AIN) which may be analogous to kidney transplant rejection. Using both clinical variables and tissue findings focusing on immune cells subtypes we evaluated a cohort of immune checkpoint inhibitor (ICI) cases to determine factors associated with renal response, progression free survival (PFS) and overall survival (OS).

Methods

We retrospectively reviewed all patients treated with ICI (2007 to 2020) at MD Anderson. A total of 35 patients with biopsy confirmed AIN were identified and immunofluorescence for CD4, CD8, CD20, and CD68 was performed on 25 cases. All slides were reviewed by two blinded board-certified renal pathologists and the severity of inflammation was graded using BANFF criteria. Patients were categorized as renal responders if creatinine improved or returned to baseline after treatment. Fisher’s exact tests for categorical variables and Wilcoxon rank-sum or Kruskal-Wallis for continuous variables were used to compare patient’s characteristics between groups. Log-rank test was performed to test the difference in survival between groups.

Results

Based on the pathological findings, patients with increased interstitial fibrosis were less likely to have renal response compared to patients with less fibrosis, (p = 0.027). Interstitial inflammation, tubulitis, number of eosinophils and neutrophils had no impact on renal response. When evaluating immune subtypes there was no strong association with response (p > 0.061). Patients with response within 3 months of AKI had a superior OS (OS rate: 77% vs 27%, p = 0.025) compared to late responders. Notably, patients who received concurrent ICI and achieved renal response within 3 months had the best OS in comparison to patients who did not receive concurrent ICI nor achieved renal response (OS rate: 100% vs 27%, p = 0.041). Similar trends were observed between response to AKI treatment and PFS.

Conclusion

This is the first analysis of ICI induced nephritis where a detailed pathological, immunological and clinical evaluation were performed to predict renal response. Our findings highlight the importance of early diagnosis and treatment of ICI-AIN while continuing concurrent ICI therapy.