Newer Cancer Therapies Offer Hope but Also May Confer Cardiac Risk

A Conversation With Jingyi Gong, MD, and Tomas Neilan, MD, MPH, FACC

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Since many different chemotherapeutic agents have been linked with cardiac adverse events, there is a growing need for strategies for the assessment and mitigation of treatment-induced cardiotoxicity. Moreover, the rapid rise of immunotherapies has added a new dimension to this clinical setting.

Jingyi Gong, MD

Jingyi Gong, MD

Tomas Neilan, MD,MPH, FACC

Tomas Neilan, MD,MPH, FACC

To shed light on this important issue, The ASCO Post spoke with Jingyi Gong, MD, and Tomas Neilan, MD, MPH, FACC. Dr. Gong is an Internal Medicine resident at the Brigham and Women’s Hospital and Dr. Neilan is a cardio-oncologist in the Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston. Drs. Gong and Neilan were authors on a recent study looking at venous thromboembolic events associated with immune checkpoint inhibitors.

Cancer Treatments and the Heart

Cardio-oncology is still a relatively new field, so before we get into your study, please give our readers an overall picture of how this field is evolving.

We agree. This is a very new field, with a simple primary focus, to work with our oncology and non-oncology colleagues to improve the cardiovascular outcomes of patients with cancer. The need for cardio-oncology is driven by multiple factors. Some include the shared risk factors and shared biology of cancer and cardiovascular disease and, for some, the understanding that certain cancer treatments may have adverse cardiovascular effects.

The insight on the effect of some of these cancer treatments on the cardiovascular system is rarely the focus of the randomized controlled trials that brought these medications to clinical oncology practice, and a lot of what we learn is from routine care. It is important to understand how these new treatments can affect cardiovascular health, to further stratify who are at risk for these adverse effects and thus who we should be more vigilant with. The next step is to understand how to prevent or treat these adverse cardiovascular events as well how conventional cardiovascular medications can help mitigate cardiovascular adverse outcomes in this special population of patients. There are many knowledge gaps.

Immune Checkpoint Inhibitors and Venous Thromboembolism

Please describe the background for your study.

Immune checkpoint inhibitors target specific negative immunologic regulators and, as a result, leverage the immune response to treat malignancy. There are limited data on the risk for venous thromboembolism (VTE) among patients on an immune checkpoint inhibitor. This knowledge gap is important, as malignancy, immune activation, and inflammation are established risk factors for VTE.

Prior to our work, some studies evaluated the combined outcome of arterial and venous thromboembolic events with the use of immune checkpoint inhibitors, with conflicting results. Therefore, we sought to describe the rates of VTE in patients treated with immune checkpoint inhibitors and compare them before and after initiation of treatment.

Study Findings

How was the study constructed, and what were the salient points?

This was a retrospective study of 2,854 patients who received immune checkpoint inhibitors at Massachusetts General Hospital. VTE events were defined as a composite of deep vein thrombosis and pulmonary embolism, which were identified by individual chart review and were blindly adjudicated using standard imaging criteria. We defined the period of exposure to immune checkpoint inhibitors (risk period) as 2 years after initiation of treatment and the control period as 2 years prior to initiation of treatment. We compared the rate of VTE events during the risk period with that during the control period.

The risk for VTE was 7.4% at 6 months and 13.8% at 1 year after starting an immune checkpoint inhibitor. Overall, the rate of VTE was more than fourfold higher after starting an immune checkpoint inhibitor. There was a 5.7-fold higher risk for deep vein thrombosis and 4.75-fold higher risk for pulmonary embolism. Comparing patients with and without a VTE event, a history of melanoma and older age predicted a lower risk of VTE, whereas a higher Khorana risk score, history of hypertension, and history of VTE predicted a higher risk.

Clinical Implications

What implications do your findings have for clinical practice?

The key message of the study findings is that patients who are treated with immune checkpoint inhibitors are at a higher risk of developing VTE after starting them. The risk for VTE was 7.4% at 6 months and 13.8% at 1 year after starting an immune checkpoint inhibitor. The higher rate for VTE events was observed for both pulmonary embolism and deep vein thrombosis. This finding highlights the need for increased clinical suspicion for VTE in patients with cancer receiving immune checkpoint inhibitors.

From a research investigation perspective, more studies are needed to consolidate the findings as well as evaluate whether prophylactic anticoagulation is indicated in this population of patients. The caveat is that the population to test would need to be carefully chosen, as some of the cancers where immune checkpoint inhibitors are especially helpful (eg, melanoma) are also cancers where bleeding risk can be higher.

Enhancing Awareness of -Cardiovascular Symptoms

Given the rise of approved immune checkpoint -inhibitors and other novel therapies that might impact cardiovascular health, are we getting better at early detection of impending symptoms and ways to address them?

For the most well-characterized cardiac toxicity induced by immune checkpoint inhibitors, myocarditis, clinicians have become more aware of early signs due to a growing body of evidence. However, for other toxicities—such as the recently described increased risk of coronary disease, VTE, pericardial disease, and ventricular arrhythmia—more data as well as more education are needed to enhance awareness, which is vital in early diagnosis. There are ongoing studies evaluating the efficacy of traditional diagnostic testing such as biomarkers (troponin) and cardiac imaging in detecting these toxicities. Within the next several years, we will continue to develop a toolbox for early diagnosis of cardiac toxicities with the use of immune checkpoint inhibitors or other novel therapies.

Closing Thoughts

Please share some closing thoughts on how cardio-oncology will evolve in the field of cancer care.

Given the rapidly developing landscape of cancer treatment, as well as evolving data describing the cardiac toxicities of these treatments, the continued collaboration between oncology and cardiology specialties will be beneficial to these patients. This is already happening at many institutions, at individual and at organizational levels. More importantly, the training of future cardiologists has started to and will continue to include cardio-oncology training. Formal advanced training will allow more cardiology-trained physicians to be equipped with the knowledge and skills to work with the cardio-oncology patient population. 

DISCLOSURE: Dr. Gong reported no conflicts of interest. Dr Neilan has served as a consultant to and received fees from Parexel Imaging, Intrinsic Imaging, H3 Biomedicine, AbbVie, Genentech, C4-Therapeutics, Roche, and Bristol Myers Squibb.