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

Overview

Journal Ther Clin Risk Manag

Publisher Dove Medical Press

Date 2025 Mar 10

PMID 40060169

Authors

Tiphaine Boucheron

Laurent Chiche

Guillaume Penaranda

Maxime Souquet

Herve Pegliasco

Julien Deturmeny

Veronique Brunel

Nicolas Barriere

Chloe Arbault-Bitton

Emilie Coquet

Laetitia Diaz

Thomas Escoda

Affiliations

Soon will be listed here.

Abstract

Background: 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.

References

Liu W, Liu Y, Ma F, Sun B, Wang Y, Luo J . Peripheral Blood Markers Associated with Immune-Related Adverse Effects in Patients Who Had Advanced Non-Small Cell Lung Cancer Treated with PD-1 Inhibitors. Cancer Manag Res. 2021; 13:765-771. PMC: 7850423. DOI: 10.2147/CMAR.S293200. View

Abbott M, Ustoyev Y . Cancer and the Immune System: The History and Background of Immunotherapy. Semin Oncol Nurs. 2019; 35(5):150923. DOI: 10.1016/j.soncn.2019.08.002. View

Diem S, Schmid S, Krapf M, Flatz L, Born D, Jochum W . Neutrophil-to-Lymphocyte ratio (NLR) and Platelet-to-Lymphocyte ratio (PLR) as prognostic markers in patients with non-small cell lung cancer (NSCLC) treated with nivolumab. Lung Cancer. 2017; 111:176-181. DOI: 10.1016/j.lungcan.2017.07.024. View

Suazo-Zepeda E, Bokern M, Vinke P, Hiltermann T, de Bock G, Sidorenkov G . Risk factors for adverse events induced by immune checkpoint inhibitors in patients with non-small-cell lung cancer: a systematic review and meta-analysis. Cancer Immunol Immunother. 2021; 70(11):3069-3080. PMC: 8505368. DOI: 10.1007/s00262-021-02996-3. View

Michot J, Bigenwald C, Champiat S, Collins M, Carbonnel F, Postel-Vinay S . Immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer. 2016; 54:139-148. DOI: 10.1016/j.ejca.2015.11.016. View

Amoroso V, Gallo F, Alberti A, Paloschi D, Ferrari Bravo W, Esposito A . Immune-related adverse events as potential surrogates of immune checkpoint inhibitors' efficacy: a systematic review and meta-analysis of randomized studies. ESMO Open. 2023; 8(2):100787. PMC: 9984799. DOI: 10.1016/j.esmoop.2023.100787. View

Scotte F, Ratta R, Beuzeboc P . Side effects of immunotherapy: a constant challenge for oncologists. Curr Opin Oncol. 2019; 31(4):280-285. DOI: 10.1097/CCO.0000000000000541. View

Wang D, Salem J, Cohen J, Chandra S, Menzer C, Ye F . Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis. JAMA Oncol. 2018; 4(12):1721-1728. PMC: 6440712. DOI: 10.1001/jamaoncol.2018.3923. View

Zhang S, Tang K, Wan G, Nguyen N, Lu C, Ugwu-Dike P . Cutaneous immune-related adverse events are associated with longer overall survival in advanced cancer patients on immune checkpoint inhibitors: A multi-institutional cohort study. J Am Acad Dermatol. 2023; 88(5):1024-1032. PMC: 10283025. DOI: 10.1016/j.jaad.2022.12.048. View

10.

Thomas M, Rognon A, Escoda T, Stavris C, Chiche L . [Expertise for management of immune-related adverse events in cancer therapy]. Bull Cancer. 2022; 110(2):244-246. DOI: 10.1016/j.bulcan.2022.11.007. View

11.

Socinski M, Jotte R, Cappuzzo F, Nishio M, Mok T, Reck M . Association of Immune-Related Adverse Events With Efficacy of Atezolizumab in Patients With Non-Small Cell Lung Cancer: Pooled Analyses of the Phase 3 IMpower130, IMpower132, and IMpower150 Randomized Clinical Trials. JAMA Oncol. 2023; 9(4):527-535. PMC: 9936386. DOI: 10.1001/jamaoncol.2022.7711. View

12.

Larkin J, Chiarion-Sileni V, Gonzalez R, Grob J, Cowey C, Lao C . Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015; 373(1):23-34. PMC: 5698905. DOI: 10.1056/NEJMoa1504030. View

13.

Pillai R, Behera M, Owonikoko T, Kamphorst A, Pakkala S, Belani C . Comparison of the toxicity profile of PD-1 versus PD-L1 inhibitors in non-small cell lung cancer: A systematic analysis of the literature. Cancer. 2017; 124(2):271-277. PMC: 5761314. DOI: 10.1002/cncr.31043. View

14.

Fujimoto A, Toyokawa G, Koutake Y, Kimura S, Kawamata Y, Fukuishi K . Association between pretreatment neutrophil-to-lymphocyte ratio and immune-related adverse events due to immune checkpoint inhibitors in patients with non-small cell lung cancer. Thorac Cancer. 2021; 12(15):2198-2204. PMC: 8327687. DOI: 10.1111/1759-7714.14063. View

15.

Liu T, Jin B, Chen J, Wang H, Lin S, Dang J . Comparative risk of serious and fatal treatment-related adverse events caused by 19 immune checkpoint inhibitors used in cancer treatment: a network meta-analysis. Ther Adv Med Oncol. 2020; 12:1758835920940927. PMC: 7394035. DOI: 10.1177/1758835920940927. View

16.

Les I, Martinez M, Perez-Francisco I, Cabero M, Teijeira L, Arrazubi V . Predictive Biomarkers for Checkpoint Inhibitor Immune-Related Adverse Events. Cancers (Basel). 2023; 15(5). PMC: 10000735. DOI: 10.3390/cancers15051629. View

17.

Long K, Suresh K . Pulmonary toxicity of systemic lung cancer therapy. Respirology. 2020; 25 Suppl 2:72-79. DOI: 10.1111/resp.13915. View

18.

Tison A, Garaud S, Chiche L, Cornec D, Kostine M . Immune-checkpoint inhibitor use in patients with cancer and pre-existing autoimmune diseases. Nat Rev Rheumatol. 2022; 18(11):641-656. DOI: 10.1038/s41584-022-00841-0. View

19.

Pavan A, Calvetti L, Dal Maso A, Attili I, Del Bianco P, Pasello G . Peripheral Blood Markers Identify Risk of Immune-Related Toxicity in Advanced Non-Small Cell Lung Cancer Treated with Immune-Checkpoint Inhibitors. Oncologist. 2019; 24(8):1128-1136. PMC: 6693718. DOI: 10.1634/theoncologist.2018-0563. View

20.

Li S, Zhang Z, Lai W, Cui L, Zhu X . How to overcome the side effects of tumor immunotherapy. Biomed Pharmacother. 2021; 130:110639. DOI: 10.1016/j.biopha.2020.110639. View