Risk of Serious Immune-Related Adverse Events with Various PD1 and PD-L1 Inhibitors: A Single-Institution, Real-Life, Comparative Study

Tiphaine Boucheron,1 Laurent Chiche,2 Guillaume Penaranda,3 Maxime Souquet,4 Hervé Pegliasco,5 Julien Deturmeny,6 Véronique Brunel,7 Nicolas Barrière,8 Chloé Arbault-Bitton,9 Emilie Coquet,1 Laetitia Diaz,1 Thomas Escoda2 1Department of Pharmacy, Hôpital Européen, Marseille, France; 2Department of Internal Medicine, Hôpital Européen, Marseille, France; 3Department of Biostatistics, Hôpital Européen, Marseille, France; 4Department of Oncology, Hôpital Européen, Marseille, France; 5Department of Pulmonology, Hôpital Européen, Marseille, France; 6Department of Urology, Hôpital Européen, Marseille, France; 7Department of Haemato-Oncology, Hôpital Européen, Marseille, France; 8Department of Gastroenterology, Hôpital Européen, Marseille, France; 9Department of Oncocardiology, Hôpital Européen, Marseille, FranceCorrespondence: Thomas Escoda, Service de Médecine Interne, Hôpital Européen, 6 rue Desirée Clary, Marseille, France, Email [email protected]: Immune checkpoint inhibitors (ICIs) are responsible for causing immune-related adverse events (irAEs). The frequency and severity of irAEs depend on various factors, but the role of the molecule used remains unclear. Our aim was to assess the comparative safety profile of different programmed cell death-1 inhibitors (anti-PD1) and programmed cell death ligand-1 inhibitors (anti-PD-L1) in a real-life setting.Methods: The occurrence of severe irAEs (grade ≥ 3) and their characteristics were recorded for all patients treated with anti-PD1 or anti-PD-L1, alone or in combination, at our center. Potential predictive factors for the occurrence of irAEs, particularly concerning the type of molecule, were identified by statistical analysis. Factors related to overall survival were also analyzed.Results: A total of 406 patients who received at least one dose of anti-PD1 (68.5%) or anti-PD-L1 (31.5%) were included, among which 60% had lung cancer. The overall frequency of the different ICIs was 51%, 17.5%, 14.3%, 12.8%, and 4.4% for pembrolizumab, nivolumab, atezolizumab, durvalumab, and avelumab, respectively. Fifty-three (13%) patients experienced severe irAEs (grade 3 or 4). While there were no significant differences with regard to ICI categories (13.7% for anti-PD1 vs 11.7% for anti-PD-L1; p = 0.5878), the rates of severe irAEs were significantly different between ICIs (29.6% for nivolumab, 22.2% for avelumab, 13.8% for atezolizumab, 8.2% for pembrolizumab, and 5.8% for durvalumab; p < 0.0001). Multivariate analyses showed that treatments with nivolumab and low polymorphonuclear neutrophil level were significant risk factors for severe irAEs. The risk of early death was lower in patients who reported severe irAEs and the risk of cancer progression was greater with one of the least toxic molecules (atezolizumab).Discussion: This study highlights the differences in toxicity profile of various ICIs targeting the PD1/PD-L1 axis in real-life use, as well as the identification of possible predictive biomarkers.Keywords: immune checkpoint inhibitor, programmed cell death-1 inhibitor, programmed cell death ligand-1 inhibitor, severe immune-related adverse event, predictive factor, toxicity