Practice patterns and outcomes in cancer patients developing immune checkpoint inhibitors–related AKI

ABSTRACT Background Acute kidney injury (AKI) is a known immune-related adverse event of cancer immune checkpoint inhibitor (ICI) therapy. Further population-based data on AKI incidence, risk factors and practice patterns post-ICI therapy are needed. Methods We measured the cumulative incidence of AKI among advanced cancer patients while receiving ICI therapy and non-ICI systemic therapy in Ontario, Canada (2012–18). An increase in serum creatinine was used to define AKI and graded according to event severity. Time to event modeling was used to compare the risk of developing AKI, pre-disposing factors and survival outcomes. Results We studied 16 425 patients with advanced cancer receiving either ICI or non-ICI systemic therapy. Among 4380 patients receiving ICI therapy, the overall crude 4-year incidence of AKI (any stage) was 29% and severe AKI (stage ≥2) was 7%. Characteristics associated with a higher risk of AKI included male sex, genitourinary (versus other) malignancy, the presence of hypertension, diabetes or chronic kidney disease, and prescription of a non-steroidal anti-inflammatory drug. The risk of experiencing AKI was significantly lower among patients treated with ICI versus non-ICI systemic therapy [adjusted hazards ratio (aHR) 0.80, 95% confidence interval (CI) 0.74–0.86, P-value <.0001]. Among the 587 patients who experienced an AKI and were both alive and discontinued ICI therapy within 30 days, 54 (9%) were re-challenged with ICI in the following 6 months and 24 (44%) had a recurrent AKI event. Patients who were re-challenged with ICI therapy had improved overall survival as compared with patients that received other non-ICI systemic therapy (aHR 0.38, 95% CI 0.22–0.67, P-value <.001). Conclusion Our real-world study demonstrates a modest risk for severe AKI among cancer patients receiving ICI therapy, lower than with exposure to other systemic cancer therapies. Among patients who developed AKI and stopped ICI therapy, re-challenge was uncommon but may warrant consideration for select patients.