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Association of medical comorbidities and cardiovascular disease with toxicity and survival among patients receiving checkpoint inhibitor immunotherapy

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Abstract

Background and objectives

Medical comorbidities (MC) are highly prevalent among patients with cancer and predict worse outcomes for traditional therapies. This association is poorly understood for checkpoint inhibitor immunotherapy (IO). We aimed to explore the relationship between common MC including cardiovascular disease (CVD), immune-related adverse events (irAEs), and overall survival (OS) among patients receiving IO for advanced cancer.

Methods

This is a retrospective cohort study of 671 patients with any cancer who received IO at our institution from 2011 to 2018. Clinical data were abstracted via chart review and query of ICD-10 codes and used to calculate modified Charlson comorbidity index (mCCI) scores. The primary outcomes were the association of individual MC with irAEs and OS using bivariate and multivariable analyses. Secondary outcomes included association of mCCI score with irAEs and OS.

Results

Among 671 patients, 62.1% had a mCCI score ≥ 1. No individual MC were associated with irAEs or OS. Increased CCI score was associated with decreased OS (p < 0.01) but not with irAEs. Grade ≥ 3 irAEs were associated with increased OS among patients without CVD (HR 0.37 [95% CI: 0.25, 0.55], p < 0.01), but not among patients with CVD.

Conclusions

No specific MC predicted risk of irAEs or OS for patients receiving IO. Increased CCI score did not predict risk of irAEs but was associated with shorter OS. This suggests IO is safe for patients with MC, but MC may limit survival benefits of IO. CVD may predict shorter OS in patients with irAEs and should be evaluated among patients receiving IO.

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Acknowledgements

The authors would like to acknowledge the contributions of Megan Reynolds and Kamila Jaroniec in the preparation of this manuscript.

Funding

Research support provided by the REDCap project and The Ohio State University Center for Clinical and Translational Science grant support (National Center for Advancing Translational Sciences, Grant UL1TR002733). This work was also supported by The National Institute of Aging (C.J.P., 1K76AG074923-01; R03AG064374) and The Ohio State University Comprehensive Cancer Center and the National Institutes of Health (P30 CA016058).

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Authors and Affiliations

  1. Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Andrew C. Johns

  2. College of Medicine, The Ohio State University, Columbus, OH, USA

    Mike Yang

  3. Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA

    Lai Wei, Daniel Spakowicz & Rebecca Hoyd

  4. Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Madison Grogan, Sandipkumar H. Patel, Mingjia Li, Marium Husain, Kari L. Kendra, Gregory A. Otterson, Jarred T. Burkart, Daniel Spakowicz, Dwight H. Owen & Carolyn J. Presley

  5. The James Cancer Hospital and Solove Research Institute, The Ohio State University Comprehensive Cancer Center, 1335 Lincoln Tower, 1800 Cannon Dr, Columbus, OH, 43210, USA

    Carolyn J. Presley

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  1. Andrew C. Johns
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Contributions

A.C.J. and C.J.P. developed the study concept and methodology. A.C.J. and M.Y. wrote the main manuscript text. L.W. performed the statistical analysis. M.Y. prepared Tables 1, 2, and 3 and Supplemental Table 1. R.H. and D.S. prepared Fig. 1. L.W. prepared Fig. 2. M.G. assisted with project administration. A.C.J, S.H.P., M.L., M.H., K.L.K., J.T.B., and D.H.O. curated patient data. All authors contributed to revision and preparation of the final manuscript text. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Carolyn J. Presley.

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Conflict of interest

Gregory Otterson reports speaker honoraria from OncLive and NCCN. He reports institution-directed research funding from: Roche/Genentech, AstraZeneca, BMS, Merck, AbbVie, and Elevation Oncology. Dwight Owen reports institution-directed research funding from BMS, Merck, Palobiofarma, Genentech, Pfizer, and Onc.AI.

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Johns, A.C., Yang, M., Wei, L. et al. Association of medical comorbidities and cardiovascular disease with toxicity and survival among patients receiving checkpoint inhibitor immunotherapy. Cancer Immunol Immunother 72, 2005–2013 (2023). https://doi.org/10.1007/s00262-023-03371-0

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