A retrospective study of characteristics and outcome of immune checkpoint inhibitor renal toxicities in a pan-cancer cohort of patients.

Abstract

e14608 Background: Renal toxicities is a known side effect of immune checkpoint inhibitors (ICI). However, our understanding of the predisposing factors and outcomes in these patients is limited. This study seeks to analyze the demographics, management, and outcomes of patients who developed immune-mediated renal toxicities. Methods: A retrospective chart review of 2723 patients who received ICIs between 2015 to 2024 was conducted. Patient demographics, therapy type, grade of toxicity, treatment and outcomes were collected. Results: In a total of 2723 patients, 37 (1.36%) developed ICI related nephritis. Primary malignancies were 35% lung, 30% kidney, 14% bladder, 11% melanoma, and 8% GI. Eighty-four percent (31/37) received palliative ICI treatment, while 17% had curative intent. Twenty (54%) patients that developed nephritis were treated with ICI combination therapy. Forty-one percent developed G1 nephritis, while 16% had G2, 38% had G3, and 8.1% had G4 nephritis which required dialysis. Of the 37 patients, 12 (32%) had concurrent toxicities with nephritis: 50% gastrointestinal, 25% arthritis/myositis, and 25% dermatitis. Patients with known renal carcinoma were found to have a fivefold higher risk of developing ICI-related nephritis compared to patients without renal carcinoma (p-value < .0001). Nephritis developed at varying times after ICI exposure, ranging from 11 days to 2.4 years, with a median of 16.5 weeks. Thirty percent of patients that developed ICI nephritis had pre-existing CKD (ranging from stage 3a to 5). There was no statistical difference of developing G3+ nephritis in baseline CKD patients compared to those without CKD (p-value 0.72). Sixty-five percent (24/37) had no improvement in kidney function after holding ICI. As the guidelines recommend, 70% (26/37) received steroids for G2-G4 nephritis. Sixty-two percent (16/26) of patients were steroid refractory and received no additional treatments. Four steroid refractory patients (10.8%) underwent renal biopsies, which showed acute interstitial nephritis. The re-challenge rate with ICI once AKI resolved was 24%. Among these patients, 78% (7/9) developed recurrent AKI and two progressed to CKD. Nephrology consults were appropriately placed for patients with G2-G4 nephritis. Forty-nine percent underwent surveillance, 19% tried another therapy, and 32% transitioned to hospice after developing nephritis. Conclusions: ICI nephritis is a rare but potentially permanent adverse effect. In this study, a majority of patients with ICI nephritis were steroid refractory. Despite guideline recommendations, no patients received additional steroid-sparing agents. We also found that ICI rechallenge is associated with recurrent renal dysfunction. Further studies are needed to elucidate risk factors and optimal treatment of ICI nephritis.