Patterns of renal toxicity from the combination of pemetrexed and pembrolizumab for advanced nonsquamous non-small-cell lung cancer (NSCLC): A single-center experience

• Published in: Lung cancer (Amsterdam, Netherlands) Vol. 174; pp. 91 - 96
• Main Authors: De Giglio, Andrea, Grandinetti, Valeria, Aprile, Marta, Borelli, Greta, Campus, Anita, Croci Chiocchini, Anna Laura, Busutti, Marco, Vischini, Gisella, Di Federico, Alessandro, Sperandi, Francesca, Melotti, Barbara, Ardizzoni, Andrea, La Manna, Gaetano, Gelsomino, Francesco
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.12.2022
• Subjects: Acute Kidney Injury - chemically induced; Acute Kidney Injury - epidemiology; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Carcinoma, Non-Small-Cell Lung - pathology; Female; Humans; Lung Neoplasms - pathology; Male; Nephritis, Interstitial - chemically induced; Nephritis, Interstitial - drug therapy; Non-small cell lung cancer; Pembrolizumab; Pemetrexed; Pemetrexed - adverse effects; Renal toxicity; Retrospective Studies; Pembrolizumab; Renal toxicity; Pemetrexed; Non-small cell lung cancer
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2022.10.007

•Platinum-pemetrexed-pembrolizumab improved survival of advanced nonsquamous non-small cell lung cancer.•The incidence of renal injury is likely higher than reported in randomized clinical trials.•The time on treatment represents the most relevant risk factor for acute renal injury.•The renal damage can be immunotherapy and/or chemotherapy dependent.•An early nephrologists consultation is pivotal to optimize the management of patients with renal impairment. The combination of immune-checkpoint inhibitors (ICI) and platinum-pemetrexed chemotherapy (CT) in first-line setting improved survival outcomes of advanced non-small cell lung cancer (NSCLC) patients. Among the various adverse events, renal toxicity can be a relevant safety issue. We conducted a single-center, observational retrospective study including consecutive patients treated with upfront CT-ICI for advanced nonsquamous NSCLC to investigate incidence and clinical characteristics of acute kidney injury (AKI) using ‘Acute Kidney Injury Working Group of Kidney Disease: Improving Global Outcomes’ (KDIGO) definition. A total of 89 patients received a first-line CT/ICI. The median age was 69 years. 60.7 % were male, and 87.6 % had an ECOG PS of 0–1. 92.1 % had a baseline glomerular filtration rate of at least 60 ml/min. According to KDIGO criteria, 25 (28 %) patients developed AKI. Considering risk factors for AKI onset, patients receiving >10 cycles of CT/ICI were more likely to experience AKI (p < 0.001). No other associations were found with other variables, including concomitant medications. Any component of the treatment was discontinued (pemetrexed pembrolizumab or both) in 10 (40 %) patients, and 9 patients (36 %) were addressed to nephrological consultation. These patients had higher mean creatinine variation from baseline (1 vs 0.6 mg/dl, p = 0.025) and creatine level (1.8 vs 1.4 mg/dl, p = 0.015), but lower eGFR (35.7 vs 54.2 ml/min, p = 0.011) in comparison to patients not addressed. No patients had microscopic hematuria or pyuria, but mild proteinuria (<0.8 g/24 h) was found in 4 patients. A renal biopsy was performed on 3 patients, revealing acute tubule interstitial nephritis (ATIN), karyomegalic interstitial nephritis, and acute tubular necrosis (ATN). Renal toxicity represents a challenging adverse event that could negatively impact outcomes of metastatic nonsquamous NSCLC patients receiving CT/ICI demanding a multidisciplinary approach.