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
Affiliations
Abdelrahman Ali
Department of Cardiology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1451, Houston, TX 77030, USA
Rebecca Caldwell
Department of Cardiology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1451, Houston, TX 77030, USA
Gaspar Pina
Department of Cardiology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1451, Houston, TX 77030, USA
Noah Beinart
Department of Cardiology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1451, Houston, TX 77030, USA
Garrett Jensen
Texas A&M College of Medicine, Center for Genomics and Precision Medicine, Houston, TX 77030, USA
Syed Wamique Yusuf
Department of Cardiology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1451, Houston, TX 77030, USA
Efstratios Koutroumpakis
Department of Cardiology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1451, Houston, TX 77030, USA
Ihab Hamzeh
Department of Cardiology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1451, Houston, TX 77030, USA
Shaden Khalaf
Department of Cardiology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1451, Houston, TX 77030, USA
Cezar Iliescu
Department of Cardiology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1451, Houston, TX 77030, USA
Anita Deswal
Department of Cardiology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1451, Houston, TX 77030, USA
Nicolas L. Palaskas
Department of Cardiology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1451, Houston, TX 77030, USA
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.
