Author + information
- Kalyan R. Chitturi, DOa,∗ (, )@KalChitturi@bhtrachtenberg,
- Jiaqiong Xu, PhDa,b,
- Raquel Araujo-Gutierrez, MDa,
- Arvind Bhimaraj, MDa,
- Ashrith Guha, MDa,
- Imad Hussain, MDa,
- Mahwash Kassi, MDa,
- Eric H. Bernicker, MDc and
- Barry H. Trachtenberg, MDa
- aHouston Methodist DeBakey Heart & Vascular Center, Houston, Texas
- bCenter for Outcomes Research, Houston Methodist Research Institute, Houston, Texas
- cDepartment of Medical Oncology, Houston Methodist Cancer Center, Houston, Texas
- ↵∗Address for correspondence:
Dr. Kalyan R. Chitturi, Houston Methodist DeBakey Heart & Vascular Center, 6550 Fannin Street, Suite 1901, Houston, Texas 77030.
Objectives The purpose of this study was to evaluate whether immune checkpoint inhibitors (ICIs) are associated with an increased risk of major adverse cardiovascular events (MACE) compared with non-ICI therapies in patients with lung cancer.
Background ICIs activate the host immune system to target cancer cells. Though uncommon, cardiovascular immune-related adverse events can be life-threatening.
Methods A retrospective single-institution cohort study of 252 patients with pathologically confirmed lung cancer who received ICI or non-ICI therapy was analyzed. The primary endpoint was MACE, defined as a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure.
Results During a median follow-up of 6 months, MACE occurred in 13.3% of ICI-treated patients, with a median time to event of 51 days, compared with 10.3% and 64 days in non-ICI patients. ICIs were not associated with MACE (hazard ratio [HR]: 1.18; 95% confidence interval [CI]: 0.57 to 2.43; p = 0.66) in a univariable Fine-Gray regression analysis incorporating noncardiovascular death as a competing risk. Multivariable regression analyses determined that patients treated with ICIs with elevated serum troponin I >0.01 ng/ml (HR: 7.27; 95% CI: 2.72 to 19.43; p < 0.001) and B-type natriuretic peptide (BNP) >100 pg/ml (HR: 2.65; 95% CI: 1.01 to 6.92; p = 0.047) had an increased risk of MACE. Patients pre-treated or receiving combined immunotherapy with ICIs and vascular endothelial growth factor inhibitors (VEGFIs) or tyrosine kinase inhibitors (TKIs) had an increased risk of MACE (HR: 2.15; 95% CI: 1.05 to 4.37; p = 0.04).
Conclusions ICIs were not independently associated with an increased risk of MACE in patients with lung cancer, although power is an important limitation in these analyses. ICI-associated cardiotoxicity was associated with elevations in serum troponin and BNP, and combined immunotherapy with VEGFIs or TKIs. Future studies are needed to further define the role of cardiac biomarkers as a monitoring strategy with ICI therapy.
Dr. Bhimaraj has been a consultant for Abbott and Abiomed. Dr. Bernicker has served on an advisory board for Guardant Health. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received August 26, 2019.
- Revision received November 10, 2019.
- Accepted November 11, 2019.
- 2019 The Authors