Clinical characteristics, time course, treatment and outcomes of patients with immune checkpoint inhibitor-associated myocarditis

Igor Puzanov; Poornima Subramanian; Yan V Yatsynovich; David M Jacobs; Maya R Chilbert; Umesh C Sharma; Fumito Ito; Steven G Feuerstein; Filip Stefanovic; Benjamin Switzer; Mark D Hicar; Anne B Curtis; Edward J Spangenthal; Grace K Dy; Marc S Ernstoff; Pankit Vachhani; Brian J Page; Nikhil Agrawal; Arjun Khunger; Ankita Kapoor; Alexander Hattoum; Jerome J Schentag

doi:10.1136/jitc-2021-002553

Clinical characteristics, time course, treatment and outcomes of patients with immune checkpoint inhibitor-associated myocarditis

J Immunother Cancer. 2021 Jun;9(6):e002553. doi: 10.1136/jitc-2021-002553.

Authors

Igor Puzanov¹, Poornima Subramanian², Yan V Yatsynovich³, David M Jacobs^{2

4}, Maya R Chilbert⁴, Umesh C Sharma³, Fumito Ito^{5

6

7}, Steven G Feuerstein^{2

4}, Filip Stefanovic^{2

8}, Benjamin Switzer⁹, Mark D Hicar¹⁰, Anne B Curtis³, Edward J Spangenthal⁹, Grace K Dy⁹, Marc S Ernstoff¹¹, Pankit Vachhani¹², Brian J Page⁹, Nikhil Agrawal¹³, Arjun Khunger¹⁴, Ankita Kapoor¹⁵, Alexander Hattoum¹⁶, Jerome J Schentag^{2

4}

Affiliations

¹ Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA igor.puzanov@roswellpark.org.
² CPL Associates, Buffalo, New York, USA.
³ Department of Medicine, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York, USA.
⁴ Department of Pharmacy Practice, University at Buffalo School of Pharmacy and Pharmaceutical Sciences, Buffalo, New York, USA.
⁵ Center for Immunotherapy, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.
⁶ Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
⁷ Department of Surgery, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, USA.
⁸ Department of Biomedical Engineering, University at Buffalo School of Engineering and Applied Sciences, Buffalo, New York, USA.
⁹ Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.
¹⁰ Department of Pediatrics, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York, USA.
¹¹ Division of Cancer Treatment and Diagnosis/Developmental Therapeutics Program, National Cancer Institute, Rockville, Maryland, USA.
¹² Department of Medicine, Division of Hematology and Oncology, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA.
¹³ Department of Cardiovascular Medicine, The University of Texas at Houston/MD Anderson Cancer Center, Houston, Texas, USA.
¹⁴ Department of Internal Medicine, Memorial Hospital West, Pembroke Pines, Florida, USA.
¹⁵ Department of Internal Medicine, Rochester General Hospital, Rochester, New York, USA.
¹⁶ Department of Cardiovascular Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.

Abstract

Background: Immune checkpoint inhibitors (ICI) have emerged as a front-line therapy for a variety of solid tumors. With the widespread use of these agents, immune-associated toxicities are increasingly being recognized, including fatal myocarditis. There are limited data on the outcomes and prognostic utility of biomarkers associated with ICI-associated myocarditis. Our objective was to examine the associations between clinical biomarkers of cardiomyocyte damage and mortality in patients with cancer treated with ICIs.

Methods: We retrospectively studied 23 patients who developed symptomatic and asymptomatic troponin elevations while receiving ICI therapy at a National Cancer Institute-designated comprehensive cancer center. We obtained serial ECGs, troponin I, and creatine kinase-MD (CK-MB), in addition to other conventional clinical biomarkers, and compared covariates between survivors and non-survivors.

Results: Among patients with myocarditis, higher troponin I (p=0.037) and CK-MB (p=0.034) levels on presentation correlated with progression to severe myocarditis. Higher troponin I (p=0.016), CK (p=0.013), and CK-MB (p=0.034) levels were associated with increased mortality, while the presence of advanced atrioventricular block on presentation (p=0.088) trended toward increased mortality. Weekly troponin monitoring lead to earlier hospitalization for potential myocarditis (p=0.022) and was associated with decreased time to steroid initiation (p=0.053) and improved outcomes.

Conclusions: Routine troponin surveillance may be helpful in predicting mortality in ICI-treated patients with cancer in the early phase of ICI therapy initiation. Early detection of troponin elevation is associated with earlier intervention and improved outcomes in ICI-associated myocarditis. The recommended assessment and diagnostic studies guiding treatment decisions are presented.

Keywords: immunotherapy.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Female
Humans
Immune Checkpoint Inhibitors / adverse effects*
Male
Middle Aged
Myocarditis / chemically induced*
Retrospective Studies

Substances

Immune Checkpoint Inhibitors

Abstract

Publication types

MeSH terms

Substances

Grants and funding