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. (November 2021)

• Record Type: Journal Article
• Authors: Hajem, Samia; Ederhy, Stéphane; Champiat, Stéphane; Troalen, Frédéric; Nolin-Lapalme, Alexis; Berhoune, Malik; Cauquil, Cécile; Martin-Romano, Patricia; Baldini, Capucine; Laparra, Ariane; Vuagnat, Perrine; Hollebecque, Antoine; Mateus, Christine; Besse, Benjamin; Naltet, Charles; Robert, Caroline; Marabelle, Aurélien; Massard, Christophe; Lambotte, Olivier; Michot, Jean-Marie
• Is Part Of: European journal of cancer. Volume 157(2021)
• Page Start: 383
• Page End: 390
• Publication Date: 2021-11
• Subjects: Creatine phosphokinase (CPK) -- Immune-related adverse events -- Immune-related myocarditis -- Immune-related myositis -- Anti-PD1 immunotherapy -- Anti-PD-L1 immunotherapy -- Immune checkpoint inhibitor -- Patient monitoring; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2021.08.045
• Languages: English
• ISSNs: 0959-8049

Abstract

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. Highlights: The increase in CPK related to immunotherapy concerned 2.7% of the patients treated. Most of the patients (61.3%) with immune-related CPK increase remained asymptomatic. The CPK increase did not generally affect the management of asymptomatic patients.