Immune related adverse events (irAEs) in patients with solid tumors and advanced chronic kidney disease (CKD) receiving checkpoint inhibitors (CPIs).

Abstract

2650 Background: Randomized controlled trials evaluating CPIs in the management of solid tumors have typically excluded patients with advanced CKD and end-stage renal disease (ESRD). Limited available data evaluating the safety of CPI use in this patient population demonstrated a similar incidence of irAEs in patients with advanced CKD compared to those with normal or mildly impaired renal function, with majority of irAEs being grade 1 or 2. CPIs are not modified by dialysis due to their molecular size and, as such, do not require renal dosing. Methods: We performed a retrospective analysis of patients over 18 years of age with solid tumors and advanced CKD, who received CPIs at the University of California Irvine from 1/2015 to 6/2021. Advanced CKD was defined as glomerular filtration rate (GFR) less than 60 ml/min. Patients must have received at least one dose of a PD-1/PD-L1 or CTLA-4 inhibitor as a single-agent or in combination with another therapy. Patients were stratified by severity of CKD, including CKD3 (GFR of 30-59 ml/min), CKD4 (GFR of 15-29 ml/min), and CKD 5/ESRD (GFR less than 15 ml/min). Results: A total of 32 patients were included, 24 (75.00%) with CKD3, 6 (18.25%) with CKD4, and 2 (6.25%) with CKD5/ESRD. 10 (31.25%) patients were female and 22 (68.75%) were male. Median age was 73.5 years [range: 26 to 98]. 22 (68.75%) received CPI monotherapy and 10 (31.25%) received a combination of CPI with another agent. After initiation of CPI therapy, 16 (50.00%) patients experienced an irAE, with a total of 23 unique irAEs due to some patients experiencing multiple irAEs. In patients with irAEs, 13 (81.25%) received CPI monotherapy and 3 (18.75%) received CPI combined with another agent. In patients with CKD3, CKD4, and CKD5/ESRD, 14 (87.50%), 2 (12.60%), and 0 (0.00%) experienced irAEs, respectively. Types of irAEs observed are listed, with the most common being colitis in 6 (26.1%) patients, endocrinopathies in 4 (17.39%) patients, and dermatologic in 4 (17.39%) patients. 18 (78.26%) of unique irAEs were grade 1 or 2, while 5 (21.74%) were grade 3 or higher. 10 (43.48%) of irAEs were managed with steroids as per physician discretion, 8 (80.00%) with CKD3 and 2 (20.00%) with CKD4. Conclusions: The safety of CPIs in patients with solid tumors and advanced CKD has not been rigorously evaluated. Recognizing the small sample size and retrospective nature of this dataset, the incidence and type of irAEs in patients with advanced CKD appears similar to that of patients with normal renal function or mild renal impairment. More prospective data in this population is needed, particularly in patients with CKD5/ESRD. Types of irAEs in patients with advanced CKD. [Table: see text]