P0216CHECK POINT INHIBITORS AND CANCER. RENAL ADVERSE EVENTS: CASE SERIES

• Published in: Nephrology, dialysis, transplantation Vol. 35; no. Supplement_3
• Main Authors: González Nuez, Selene, Pérez Suárez, Germán, Ramírez Puga, Ana, Rodríguez Abreu, Delvys, Fernández Granados, Saulo Jesús, Esparza Martín, Noemí, García Cantón, César
• Format: Journal Article
• Language: English
• Published: Oxford University Press 01.06.2020
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfaa142.P0216

Abstract Background and Aims The treatment of cancer with check point inhibitors (CPI) has demonstrated significant benefits. CPI initiate antitumor immunity through negative regulatory components in T cells. However, these agents are associated with adverse events related to the immune system that can affect several organs. Initially, a low incidence of renal adverse events was reported, although recent data suggest an incidence between 9.9% and 29%. The objective of the study was to describe a case series that presented renal dysfunction related to CPI treatment. Method 11 patients were studied retrospectively (67% males, mean age 69 ± 13 years), diagnosed with Neoplasms (9 advanced lung cancer, 7 of them metastatic and 2 metastatic melanomas) treated with CPI, who developed renal dysfunction. 5 patients with lung cancer were treated with Pembrolizumab, 3 with Nivolumab and 1 with Pembrolizumab + Ipilimumab combination. Patients with melanoma received Pembrolizumab. In 55% of the cases, immunotherapy was used as first line of antitumor treatment. Demographic and clinical-analytical data were collected, as well as the evolution of renal function. Results The median plasma creatinine prior to receiving treatment with CPI was 0.9 mg/dl [0.67-1.5]. The maximum creatinine reached after treatment with CPI was 2.5 mg/dl [1.8-7.5] with Pembrolizumab, 5.4 mg/dl [3-6.7] with Nivolumab and 4.3 mg/dl with the combination Pembrolizumab + Ipilimumab. Renal dysfunction occurred in the fifth cycle of treatment with Pembrolizumab and in the third cycle with Nivolumab and Pembrolizumab + Ipilimumab. All patients received steroids (1mg/kg) and CPI were permanently discontinued in 3 patients with Pembrolizumab (43%), 1 with Nivolumab (33.3%) and 1 with Pembrolizumab + Ipilimumab (100%). Renal biopsy was performed in 4 patients who initially did not respond to steroids, resulting in acute tubulo-interstitial nephritis (ATIN), 1 of them with granuloma formation and worse renal evolution. All patients recovered renal function partially or totally, except 1 treated with Pembrolizumab who remained with advanced kidney disease. Tumor progression was observed in 3 patients and 2 died. Conclusion CPI have demonstrated significant clinical benefits in the regression and prolonged stabilization of many tumors. The main cause of renal dysfunction after the use of CPI in our patients was the ATIN, with a good initial response to steroids and drug suspension. The presence of granulomas in renal biopsy confers a poor prognosis. It is an increasingly frequent entity in clinical practice, and because of its complicated management, it requires a multidisciplinary approach.