1. Absence of significant clinical benefit for a systematic routine creatine phosphokinase measurement in asymptomatic patients treated with anti-programmed death protein (ligand) 1 immune checkpoint inhibitor to screen cardiac or neuromuscular immune-related toxicities.
- Author
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Hajem S, Ederhy S, Champiat S, Troalen F, Nolin-Lapalme A, Berhoune M, Cauquil C, Martin-Romano P, Baldini C, Laparra A, Vuagnat P, Hollebecque A, Mateus C, Besse B, Naltet C, Robert C, Marabelle A, Massard C, Lambotte O, and Michot JM
- Subjects
- B7-H1 Antigen antagonists & inhibitors, Biomarkers blood, Cardiotoxicity blood, Cardiotoxicity immunology, Feasibility Studies, Female, Humans, Male, Memory, Episodic, Middle Aged, Neoplasms blood, Neuromuscular Diseases blood, Neuromuscular Diseases chemically induced, Neuromuscular Diseases immunology, Programmed Cell Death 1 Receptor antagonists & inhibitors, Retrospective Studies, Cardiotoxicity diagnosis, Creatine Kinase blood, Immune Checkpoint Inhibitors adverse effects, Neoplasms drug therapy, Neuromuscular Diseases diagnosis
- Abstract
Aim: Despite unprecedented results of anti-programmed death protein (ligand) 1 (PD-(L)1) immune checkpoint inhibitor in the oncology's armamentarium, immune-related adverse events (irAEs) represent a therapeutic hurdle. Currently, there is no consensual recommendation on a routinely monitored biomarker to early detect irAE. Biological markers such as serum creatine phosphokinase (CPK) are commonly used to measure muscular tissue injury. The potential of routine serum CPK monitoring to predict cardiac or neuromuscular irAE in patients treated with immunotherapy remains unknown., Methods: In this retrospective study between January 2016 and December 2018 at Gustave Roussy Cancer Campus, 1151 cancer patients treated with anti-PD-(L)1 immunotherapy were systematically monitored with serum CPK measurements before each immunotherapy cycle. We considered significant CPK increases according to Common Terminology Criteria for Adverse Events v5.0 (CTCAEV5) of grade ≥2 severity. Comparisons were performed in patients with immune-related CPK (ir-CPK) elevations symptomatic versus asymptomatic., Results: Overall, 53 of 1151 (4.6%) patients showed a CPK increase. Elevations of CPK were deemed to be immunotherapy-related in 31 of 1151 (2.7%) patients. Among them, 12 of 31 (38.7%) patients experienced symptomatic cardiac or neuromuscular irAE, whereas the other 19 of 31 (61.3%) patients remained asymptomatic. In patients with symptomatic irAE, the mean ir-CPK level was higher compared with asymptomatic patients (1271 versus 771 UI/L, P value = 0.02). In the asymptomatic group, all patients experienced a spontaneous resolution of the ir-CPK increase, and none required medical intervention., Conclusion: Most patients with immune-related CPK increase remained asymptomatic. The CPK serum increase did not alter the clinical management of asymptomatic patients. The results of this study did not support a significant clinical interest for a systematic routine CPK monitoring in patients amenable to anti-PD-(L)1 immunotherapy., Competing Interests: Conflict of interest statement S.H. declares that she has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article. J.-M.M. declares that in the last 5 years, he has been the principal investigator or the subinvestigator of clinical trials for Abbvie, Agios, Amgen, Astex, AstraZeneca, Blueprint, BMS, Celgene, Forma, Genentech, GSK, H3 biomedecine, Incyte, Innate Pharma, Janssen, Lilly, Medimmune, MSD, Nektar Therapeutics, Novartis, Oncopeptides AB, Pfizer, Pharmamar, Roche, Sanofi, Seattle Genetics, Sierra Oncology and Xencor. All the remaining authors have declared no conflicts of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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