Defining the spectrum of CV effects of immune checkpoint inhibitors

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The study covered in this abstract was posted on ResearchSquare.com as a preprint and has not yet been peer-reviewed.

Key points to remember

  • Immune checkpoint inhibitors (ICIs) are a widely used and effective treatment for many cancers, but their full range of cardiovascular (CV) complications is not well understood.

  • Among the spectrum of CV complications associated with ICI treatment, myocarditis is the most common, but atrial tachyarrhythmias, noninflammatory left ventricular dysfunction (NILVD), and other conditions are also possible.

why it matters

  • The study describes real-world experiences in diagnosing and managing a range of cardiac complications in cancer patients who receive ICI treatment.

  • The number of patients with these complications may well increase as the number of licensed indications for ICI increases, as cardiologists and oncologists become more aware of the wide range of cardiac events, and as more cancer patients survive and receive longer treatments for ICI.

study design

  • In the retrospective analysis, 110 patients out of a total of 2647 under ICI treatment were referred to the cardio-oncology department with possible CV complications from 2014 to 2020.

  • Patients were included if they had active cancer treated with ICI at baseline and new CV disease without further explanation.

  • Other exclusion criteria included no CV complications when assessed by the cardio-oncology department, loss to follow-up before completion of their CV assessment, referral for assessment of CV disease pre-existing disease and the gold standard for monitoring the response to ICI treatment of an intracardiac metastasis.

  • Of the 89 patients included in the final analysis, 55% were men and their median age was 63 years.

Principle results

  • The most common primary cancer was melanomaobserved in 30% of patients, followed by urinary tract cancer in 23% of patients and lung cancer in 16%.

  • Anti-programmed cell death protein 1 antibody pembrolizumab was the most frequently prescribed ICI, used in 28 patients; followed by combined treatment with ipilimumab and nivolumab in 24 patients; and single ICI therapy with nivolumab in 13, durvalumab in 10, and atezolizumab in nine patients.

  • Myocarditis was the most common CV complication, occurring in 33 patients. Of these, 51% had definite myocarditis, 29% probable myocarditis and 20% possible myocarditis according to published criteria. High dose steroids were used in 73% of patients.

  • Atrial or ventricular tachyarrhythmias were the most common cardiac event and were observed in 30 patients. Of these, 12 were treated with anticoagulation, rate control drugs, or ablation if necessary.

  • NILVD in the absence of myocarditis, ischemia, infarction or other acute causes was observed in 15 patients. Of these, 73% were treated with angiotensin converting enzyme inhibitors or angiotensin receptor blockers, and 47% were put on beta-blockers. ICI therapy was restarted safely in 11 patients.

  • Other CV complications included pericarditis in seven patients, ischemic heart disease due to microvascular dysfunction or acute coronary syndrome in six patients, vasovagal syncope in four patients, bradyarrhythmia in four, new pulmonary artery hypertension in two, and cytokine release syndrome in one patient.

Limits

  • The single-center observational study had potential for baseline bias, and some CV complications may have been missed.

  • A matched, untreated control cohort was not available.

  • Some data regarding ICI treatment before the development of adverse events are not always available.

Disclosures

  • The study was funded by the Royal Brompton Hospital Charity and the Leducq Foundation Cardio-Oncology Network of Excellence.

  • One author reported receiving speaker, advisory or consulting fees and/or research grants from Pfizer, Novartis, Servier, AstraZeneca, Bristol-Myers Squibb, GSK, Amgen, Takeda, Roche, Janssens-Cilag, Ltd, Clinigen Group, Eli Lily, Eisai, Ltd, Ferring Pharmaceuticals, Boehringer Ingelheim, Akcea Therapeutics, Myocardial Solutions, iOWNA Health and Heartfelt Technologies, Ltd. The other authors made no disclosures.

This is an abstract of a preprint research study, “The Spectrum of Cardiovascular Complications Associated with Immune Checkpoint Inhibitor Therapy“, written by Maria Sol Andres, Royal Brompton Hospital, Guy’s and St. Thomas’ NHS Foundation Trust, and colleagues on ResearchSquare.com, provided by Medscape. This study has not yet been peer-reviewed. The text full study can be viewed on ResearchSquare.com.

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