#2520 Rechallenge of immune checkpoint inhibitors in cancer patients with biopsy-confirmed renal injury: a case series

Abstract Background and Aims Acute kidney injury (AKI) is a possible immune related adverse event (IRAE) of immunotherapy on cancer patients. Rechallenging with immune checkpoint inhibitors (ICIs) after acute kidney injury is a complex clinical decision with potential risks and benefits. Current data on the timing and the outcomes of rechallenge following AKI are sparse, but the potential benefits of continued ICI therapy may outweigh the risks of rechallenge, especially if there are limited alternative treatment options. Method We assessed the records of all patients from January 2020 to February 2024 that were treated with ICIs, developed biopsy proven kidney injury associated with immunotherapy and then after the resolution of kidney injury they were rechallenged with ICI. Results We included 7 patients, 5 males and 2 females, with mean age at the time of kidney biopsy 66 years, and median follow up time 13 months. The most common primary malignancy was non-small cell lung carcinoma (n = 6) and there was one case of renal cell carcinoma (n = 1). Most patients (n = 6) were treated with the PD-1 inhibitor pembrolizumab, and one patient received a combination of two checkpoint inhibitors ipilimumab and nivolumab. Four patients were also treated with chemotherapy apart from ICI, and one also received targeted therapy (axitinib). Six patients were presented with AKI [AKI stage 2 KDIGO (n = 4), AKI stage 3 (n = 2)] and one patient with severe nephrotic syndrome. The median time to developing kidney injury from immunotherapy initiation was 13 months. Five patients also developed extrarenal immune related adverse events (IRAEs) during the follow-up time. Dermatitis (n = 3) and pneumonitis (n = 2) were the most common followed by hepatitis (n = 1) and colitis (n = 1). Renal biopsy showed acute interstitial nephritis (AIN) in 2 patients, acute tubular injury (ATI) in 2 patients, mixed ATI/AIN in one patient, ATI with diabetic nephropathy in one patient and membranous nephropathy (MN) with a lupus-like pattern in immunofluorescence in the patient with nephrotic syndrome. All patients received corticosteroids (prednisone 1 mg/kg) empirically. Prednisone was withdrawn in patients with ATI and DN/ATI. Immunotherapy was temporarily withheld. All patients experienced recovery of kidney function 2 months after the initiation of prednisone (among them the patient with DN/ATI who required renal replacement therapy at the time of biopsy) and the patient with nephrotic syndrome experienced partial remission of proteinuria. After rechallenging, five patients continued ICI treatment without recurrence of kidney injury until the end of follow-up time. The patient with DN/ATI developed severe pneumonitis one month after rechallenging that required reinitiation of corticosteroids and the patient with MN experienced proteinuria relapse, so immunotherapy was withdrawn in both patients. Conclusion Reintroducing immunotherapy after AKI is feasible in selected cases after timely diagnosis and therapy of renal injury, especially when there is lack of alternative oncological treatment options and it requires close collaboration among nephrologists and oncologists to continue ICI therapy while safeguarding renal health.