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
1908 - Androgen Receptor (AR) Aberrations in Patients (Pts) With Metastatic Castration-Sensitive Prostate Cancer (mCSPC) Treated With Apalutamide (APA) Plus Androgen Deprivation Therapy (ADT) in TITAN
Presenter: Kim Chi
Session: Poster Display session 3
Resources:
Abstract
4058 - 68Ga-PSMA guided bone biopsies for molecular diagnostics in metastatic castration resistant prostate cancer patients
Presenter: Anouk de Jong
Session: Poster Display session 3
Resources:
Abstract
2226 - Spatial-Temporal Change in Quantitative Total Bone Imaging (QTBI) and Circulating Tumor Cells (CTCs) in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated With Enzalutamide (ENZA)
Presenter: Glenn Liu
Session: Poster Display session 3
Resources:
Abstract
5795 - Efficacy of Enzalutamide in Hormone-sensitive Metastatic Prostate Cancer: Clinical Utility of 18F-Choline PET and Whole Body MRI.
Presenter: Susanne Osanto
Session: Poster Display session 3
Resources:
Abstract
899 - Urine extracellular vesicle GATA2 mRNA alone and in a multigene test predicts initial prostate biopsy result
Presenter: Jungreem Woo
Session: Poster Display session 3
Resources:
Abstract
3094 - Circulating tumor cell (CTC) genomic landscape in neuroendocrine prostate cancer (NEPC) by single cell copy number analysis
Presenter: Vincenza Conteduca
Session: Poster Display session 3
Resources:
Abstract
2527 - Circulating Tumor Cells (CTC) count and Prostate-Specific Antigen (PSA) response measures in metastatic Castration-Resistant Prostate Cancer (mCRPC) patients (pts) treated with Docetaxel (Doc)
Presenter: Rebeca Lozano Mejorada
Session: Poster Display session 3
Resources:
Abstract
6106 - Assessing the clinical relevance of drug–drug interactions (DDI) with darolutamide (DARO)
Presenter: Christian Zurth
Session: Poster Display session 3
Resources:
Abstract
2237 - KEYNOTE-921: phase 3 study of pembrolizumab (pembro) plus docetaxel and prednisone for enzalutamide (enza)- or abiraterone (abi)-pretreated patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).
Presenter: Daniel Petrylak
Session: Poster Display session 3
Resources:
Abstract
2241 - KEYNOTE-641: Phase 3 Study of Pembrolizumab (pembro) Plus Enzalutamide for Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Presenter: Julie Graff
Session: Poster Display session 3
Resources:
Abstract