Adverse drug reactions associated with immune checkpoint inhibitors: An exploratory nested case-control study in a historical cohort

Manon Pluye; Aurore Gouraud; Magali Herve; Ha Le; Tristan Dagonneau; Stéphane Dalle; Judith Cottin; Michel Cucherat; Marina Atzenhoffer

doi:10.1016/j.therap.2022.07.001

Adverse drug reactions associated with immune checkpoint inhibitors: An exploratory nested case-control study in a historical cohort

Therapie. 2023 May-Jun;78(3):303-311. doi: 10.1016/j.therap.2022.07.001. Epub 2022 Jul 8.

Authors

Manon Pluye¹, Aurore Gouraud¹, Magali Herve¹, Ha Le¹, Tristan Dagonneau², Stéphane Dalle³, Judith Cottin¹, Michel Cucherat⁴, Marina Atzenhoffer⁵

Affiliations

¹ Service Hospitalo-Universitaire de Pharmaco-Toxicologie (SHUPT), Hospices civils de Lyon, 162, avenue Lacassagne, 69424 Lyon, France.
² Department of Medical Information, Centre Hospitalier Lyon-Sud, 69495 Lyon, France.
³ Hospices civils de Lyon, Cancer Research Center of Lyon, Dermatology Department, Pierre-Bénite, France; Université Lyon 1, ImmuCare (Immunology Cancer Research), 69100 Villeurbanne, France.
⁴ Service Hospitalo-Universitaire de Pharmaco-Toxicologie (SHUPT), Hospices civils de Lyon, 162, avenue Lacassagne, 69424 Lyon, France; UMR 5558 CNRS Lyon, Université de Lyon, Université Lyon 1, 69003 Lyon, France.
⁵ Service Hospitalo-Universitaire de Pharmaco-Toxicologie (SHUPT), Hospices civils de Lyon, 162, avenue Lacassagne, 69424 Lyon, France. Electronic address: marina.atzenhoffer@chu-lyon.fr.

PMID: 35906145
DOI: 10.1016/j.therap.2022.07.001

Abstract

Introduction: Data on adverse drug reactions (ADRs) of immune checkpoint inhibitors (ICIs) used in oncology are mainly derived from clinical trials or cancer-specific reviews. We aim to analyze ADRs that occurred in patients treated with ICIs in real life.

Materials and methods: We conducted an observational study on a historical cohort of the University Hospitals of Lyon. All patients who initiated an ICI treatment for any cancer in 2017 were included. Patients were followed from the first infusion until 90 days after the last one, death, date of last news or end of the study period (28 February 2019), whichever came first. Two pharmacovigilance specialists assessed the accountability and the severity of each ADR using Naranjo algorithm and common terminology criteria for adverse events (CTCAE) classification, respectively.

Results: 248 patients were included. They were treated with anti-PD-(L)-1, mainly nivolumab (70.6%) and pembrolizumab (25.8%). Lung cancer (62.1%) and melanoma (20.2%) were the most represented cancers. 139 ADRs occurred in 93 patients (37.5%), on average at the 6^th cure (±6.8). ADRs mainly concerned skin (29.5%), endocrine (19.4%) and digestive (10.8%) systems. 17.3% of ADRs were grades III-V and two patients died because of ADRs. By comparing patients with (N=93) or without (N=155) ADRs, all characteristics appeared similar except for age, number of infusions received and death status. The spontaneous notification rate found in this study was 5.8% for all grade ADRs (N = 8) but raised to 23.8% when only grades higher than III were considered (N = 5).

Discussion/conclusion: Our results are consistent with literature data in frequency and type of serious ADRs. We found a lower frequency of ADRs of any grade, which could be explained by a fairer causality assessment in our study than in clinical trials.

Keywords: Adverse drug reaction; Cancer; Immune checkpoint inhibitor; Immunotherapy; Oncology; Real life data.

Publication types

Observational Study

MeSH terms

Adverse Drug Reaction Reporting Systems
Case-Control Studies
Drug-Related Side Effects and Adverse Reactions* / epidemiology
Humans
Immune Checkpoint Inhibitors / adverse effects
Melanoma*
Pharmacovigilance

Substances

Immune Checkpoint Inhibitors