Patients with AKI can be rechallenged with immune checkpoint inhibitors
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Patients with AKI may continue treatment with immune checkpoint inhibitors, even if they have experienced immune checkpoint inhibitor-AKI, according to data published in the Journal for ImmunoTherapy of Cancer.
While immune checkpoint inhibitors (ICPis) are widely used as anticancer treatment, these can cause various immune-related adverse events (irAEs), including ICPi-associated AKI (ICPi-AKI). Currently, there are limited data on the safety of rechallenging patients with ICPis following an episode of ICPi-AKI.
“ICPi-AKI is one of the most consequential irAEs that occurs in cancer patients receiving ICPi therapy,” Shruti Gupta, MD, MPH, nephrologist from the Brigham and Women’s Hospital, told Healio. “Development of ICPi-AKI can have important implications for patients, including cessation of ICPi therapy and often a prolonged course of immunosuppression. However, data on ICPi-AKI are largely limited to case reports, small case series and single-center studies.”
In an international multicenter cohort study, Gupta and colleagues collected data from 429 patients with ICPi-AKI (median age, 68; 62% men; 81.8% white) and 429 control patients who received ICPis at the same time but did not develop ICPi-AKI (median age, 65; 58.5% men; 81.6% white). These patients came from 30 sites across 10 countries and were diagnosed with ICPi-AKI between 2012 and 2020.
Using multivariable logistic regression, researchers identified predictors of ICPi-AKI and its recovery. Additionally, researchers utilized a multivariable Cox model to predict the effect of ICPi rechallenge vs. no rechallenge on survival after ICPi-AKI.
Researchers found that ICPi-AKI transpired at a median of 16 weeks after ICPi initiation, and there was no difference in survival among those rechallenged vs. those not rechallenged after ICPi-AKI.
Patients who developed ICPi-AKI were more likely to show impaired renal function at baseline, use a proton pump inhibitor and have extrarenal irAEs. Data revealed that 64.3% of patients experienced renal recovery at a median of 7 weeks after ICPi-AKI. Those treated with corticosteroids within 2 weeks of ICPi-AKI diagnosis correlated with higher odds of renal recovery (adjusted OR = 2.64; 95% CI, 1.58 to 4.41).
According to the press release, “One of the most important findings from the 2-year study reveals that among patients who take ICPi again — even after an episode of ICPi-AKI — only 16.5% developed recurrent ICPi-AKI, which shows that most patients can still take these life-saving medications safely.”
“Our data highlight important risk factors for ICPi-AKI,” Gupta told Healio. “For instance, oncologists and nephrologists should be aware of the association between proton pump inhibitor use and ICPi-AKI. It's important to recognize that there are no clinical features or laboratory findings that are sensitive or specific for ICPi-AKI, though the presence of extrarenal immune-related adverse events should raise suspicion for ICPi-AKI in the proper context. Our data also highlight the importance of early initiation of corticosteroids in patients with suspected ICPi-AKI. Perhaps most importantly, our finding that so few patients developed recurrent ICPi-AKI after ICPi rechallenge suggests that rechallenge should be considered in these patients.”
“We hope that this research around ICPi-AKI will help shed light on those risks, treatment potential and prognosis for those who may develop ICPi-AKI,” Rimda Wanchoo, MD, nephrologist and co-author on the paper, said in the press release.
Future studies with longitudinal biospecimen collection and randomized clinical trials are needed to further evaluate the mechanisms of ICPi-AKI and efficacy of corticosteroid doses, researchers noted.
Reference:
- New study shows prevalence, treatment outcomes for acute kidney injury from anticancer drugs. https://www.northwell.edu/news/the-latest/new-study-shows-prevalence-treatment-outcomes-for-acute-kidney-injury-from-anticancer-drugs. Published Oct. 8, 2021. Accessed Oct. 26, 2021.
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