Elevated IL-6 and Tumor Necrosis Factor-α in Immune Checkpoint Inhibitor Myocarditis

Abdelrahman Ali; Rebecca Caldwell; Gaspar Pina; Noah Beinart; Garrett Jensen; Syed Wamique Yusuf; Efstratios Koutroumpakis; Ihab Hamzeh; Shaden Khalaf; Cezar Iliescu; Anita Deswal; Nicolas L Palaskas

doi:10.3390/diseases12050088

Elevated IL-6 and Tumor Necrosis Factor-α in Immune Checkpoint Inhibitor Myocarditis

Diseases. 2024 May 3;12(5):88. doi: 10.3390/diseases12050088.

Affiliations

¹ Department of Cardiology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1451, Houston, TX 77030, USA.
² Texas A&M College of Medicine, Center for Genomics and Precision Medicine, Houston, TX 77030, USA.

Abstract

Introduction: The impact of peripheral cytokine levels on the prognosis and treatment of immune checkpoint inhibitor (ICI) myocarditis has not been well studied.

Objectives: This study aimed to identify cytokines that can prognosticate and direct the treatment of ICI myocarditis.

Methods: This was a single-center, retrospective cohort study of patients with ICI myocarditis who had available peripheral cytokine levels between January 2011 and May 2022. Major adverse cardiovascular events (MACEs) were defined as a composite of heart failure with/without cardiogenic shock, arterial thrombosis, life-threatening arrhythmias, pulmonary embolism, and sudden cardiac death.

Results: In total, 65 patients with ICI myocarditis had cytokine data available. Patients were mostly males (70%), with a mean age of 67.8 ± 12.7 years. Interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) were the most common cytokines to be elevated with 48/65 (74%) of patients having a peak IL-6 above normal limits (>5 pg/mL) and 44/65 (68%) of patients with peak TNF-α above normal limits (>22 pg/mL). Patients with elevated peak IL-6 had similar 90-day mortality and MACE outcomes compared to those without (10.4% vs. 11.8%, p = 0.878 and 8.8% vs. 17.7%, p = 0.366, respectively). Similarly, those with elevated peak TNF-α had similar 90-day mortality and MACEs compared to those without (29.6% vs. 14.3%, p = 0.182 and 13.6% vs. 4.8%, p = 0.413, respectively). Kaplan-Meier survival analysis also showed that there was not a significant difference between MACE-free survival when comparing elevated and normal IL-6 and TNF-α levels (p = 0.182 and p = 0.118, respectively). MACEs and overall survival outcomes were similar between those who received infliximab and those who did not among all patients and those with elevated TNF-α (p-value 0.70 and 0.83, respectively).

Conclusion: Peripheral blood levels of IL-6 and TNF-α are the most commonly elevated cytokines in patients with ICI myocarditis. However, their role in the prognostication and guidance of immunomodulatory treatment is currently limited.

Keywords: Cardiotoxicity; Cytokines; Immunotherapy; Myocarditis.

Grants and funding

This work was supported by the Cancer Prevention & Research Institute of Texas (CPRIT) RP200670. Dr. Palaskas is supported by the Cancer Prevention & Research Institute of Texas (CPRIT) RP200670, NIH/NCI 1P01CA261669-01, Andrew Sabin Family Foundation, Replimmune, Kiniksa Pharma-ceuticals. Dr. Deswal is supported in part by the Ting Tsung and Wei Fong Chao Distinguished Chair.