Abstract 3468
Background
Anti-PD1 and anti-PD-L1 are effective checkpoints inhibitors to stimulate the immune system against many types of cancers. The flip side of these immunotherapies is the generation of immune-related adverse events (irAE), which can theoretically affect all organs including muscle tissue. Immune-related creatine phosphokinase (irCPK) increase is associated with immune related myositis. The meaning of CPK monitoring in clinical practice remains poorly understood. In this observational study, all the grade ≥ 2 increased CPK occurring in patients treated with anti-PD-1 or anti-PD-L1 were investigated to determine their clinical significance.
Methods
All consecutive pts treated with anti-PD1 or anti-PD-L1, in monotherapy or in combine therapy with other agents, monitored by routine CPK in the Drug Development Department (DITEP) and in the Dermatology Unit of Gustave Roussy between January 2016 and December 2018 were retrospectively reviewed. Patients CPK monitoring level were extracted from biological chart and all the patients with grade ≥ 2 increased CPK were selected for the analysis.
Results
Among the 1151 patients treated with anti PD1/PD-L1, 53 (4.6%) had grade ≥ 2 increased CPK regardless of immune causality and 31 (2.7%) had a grade ≥ 2 irCPK increase. Among the 53 pts with CPK increase, mean age was 54 years old, tumor types were skin (n = 21), bladder and urothelial (n = 5), head and neck (n = 4) and others (n = 23). CPK increase was not related to the treatment in 22 (41%) pts, was immune-related to anti-PD1/PDL1 and not clinically significant in 19 (36%) pts, was immune-related with muscular adverse events in 10 (19%) pts, including 2 myositis and 2 acute polyradiculoneuritis; and was immune-related with myocarditis in 2 (4%) pts. The mean of CPK maximal peak was significantly higher in patients with immune-related cardiac or muscular adverse event that in the asymptomatic CPK increase pts (1271 UI/L vs. 771 UI/L, p-value = 0.02).
Conclusions
The frequency of grade ≥ 2 irCPK increase is estimated at 2.7% of patients treated with anti-PD1 or anti-PD-L1. For patients treated with anti PD1/PD-L1, regular CPK monitoring appears as clinically relevant in the early detection of immune-related cardiac and muscular adverse events.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Jean-Marie Michot.
Funding
Has not received any funding.
Disclosure
C. Baldini: Advisory / Consultancy: Consultant/Advisory fees from Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion Principal/sub-Investigator of Clinical Trials for AbbVie, Aduro. P. Romano-Martin: Advisory / Consultancy: Consultant/Advisory fees from Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion Principal/sub-Investigator of Clinical Trials for AbbVie, Aduro. P. Vuagnat: Advisory / Consultancy: Consultant/Advisory fees from Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion Principal/sub-Investigator of Clinical Trials for AbbVie, Aduro. S. Champiat: Advisory / Consultancy: Consultant/Advisory fees from Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion Principal/sub-Investigator of Clinical Trials for AbbVie, Aduro. A. Varga: Advisory / Consultancy: Consultant/Advisory fees from Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion Principal/sub-Investigator of Clinical Trials for AbbVie, Aduro. A. Hollebecque: Advisory / Consultancy: Consultant/Advisory fees from Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion Principal/sub-Investigator of Clinical Trials for AbbVie, Aduro. C. Robert: Advisory / Consultancy: Roche, BMS, MSD, Amgen, Novartis. C. Massard: Advisory / Consultancy: Consultant/Advisory fees from Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion Principal/sub-Investigator of Clinical Trials for AbbVie, Aduro. O. Lambotte: Advisory / Consultancy: BMS, MSD, AstraZeneca, LFB, CSL Behring, Janssen. J. Michot: Advisory / Consultancy: Consultant/Advisory fees from Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion Principal/sub-Investigator of Clinical Trials for AbbVie, Aduro. All other authors have declared no conflicts of interest.
Resources from the same session
2108 - Biomarker analyses of ramucirumab in patients with platinum refractory urothelial cancer from RANGE, a global, randomized, double-blind, phase 3 study.
Presenter: Michiel Van der Heijden
Session: Poster Display session 3
Resources:
Abstract
3090 - Comparison of Immuno-Oncology (IO) Biomarkers in Adenocarcinoma (ACB), Urothelial Carcinoma (UCB) and Squamous Cell Carcinoma (SCCB) of the Bladder, with interim results from PURE01
Presenter: Daniele Raggi
Session: Poster Display session 3
Resources:
Abstract
5211 - Potential role of a clinical, taxonomical classification and RNA expression integrated signature to predict response to neoadjuvant platinum-based chemotherapy in muscle-invasive bladder cancer (MIBC) patients
Presenter: Albert Font
Session: Poster Display session 3
Resources:
Abstract
3206 - Hyperphosphatemia due to Erdafitinib (a Pan-FGFR Inhibitor) and Anti-tumor Activity Among Patients (Pts) with Advanced Urothelial Carcinoma (UC)
Presenter: Scott Tagawa
Session: Poster Display session 3
Resources:
Abstract
3110 - Prognostic role of FGFR Mutations and FGFR mRNA expression in metastatic urothelial cancer treated with anti-PD(L1) inhibitors in first and second line setting
Presenter: Florian Roghmann
Session: Poster Display session 3
Resources:
Abstract
3564 - Circulating tumour DNA (ctDNA) utility as a biomarker for metastatic urothelial carcinoma (mUC)
Presenter: Jean-Michel Lavoie
Session: Poster Display session 3
Resources:
Abstract
2760 - Comparative analysis of tumor mutational burden (TMB) prediction methods and its association with determinants of the tumor immune microenvironment of urothelial bladder cancer (UBC)
Presenter: Markus Eckstein
Session: Poster Display session 3
Resources:
Abstract
2513 - The Immunoscore in patients with urothelial carcinoma treated with neoadjuvant chemotherapy: clinical significance for pathological response and survival
Presenter: Elise Nassif
Session: Poster Display session 3
Resources:
Abstract
2835 - Genomic analysis of urothelial cancer and associations with treatment choice and outcome
Presenter: David Sarid
Session: Poster Display session 3
Resources:
Abstract
5763 - cfDNA is an acceptable but insufficient means of characterizing FGFR3 mutation in patients with metastatic urothelial cancer (mUC)
Presenter: Sumanta Pal
Session: Poster Display session 3
Resources:
Abstract