To stop or not to stop: that is the question - resuming immunotherapy in cancer patients on immune checkpoint inhibitors treatment following atherosclerosis-related acute cardiovascular events

A growing body of research indicates that immune checkpoint inhibitors (ICIs) may have pro-atherogenic side effects that increase the risk of atherosclerotic cardiovascular disease (ASCVD) in cancer patients receiving long-term treatment.

Data on ASCVD [coronary artery disease (CAD), peripheral artery disease (PAD), cerebrovascular disease (CVD), and aortic atherosclerosis (AA)] in active cancer patients who had been receiving ICIs for at least six months at our institution in the past four years were collected. Information about ASCVD diagnosis, management, and outcomes, as well as baseline information on cancer site, ICI type, treatment line, and physician attitude on the continuation of ICIs following acute events, were recorded.

40 patients were identified (29/11 M/F; median age 72[59-82]years), 31 with CAD [21 non-ST-segment elevation myocardial infarction (NSTEMI), 6 ST-segment elevation myocardial infarction (STEMI), 4 unstable angina (UA)], 8 with CVD (all ischemic stroke) and 1 PAD. Cases were all treated according to guidelines with medical therapy and appropriate invasive strategies (coronary angiography and PTCA-stenting for CAD and peripheral angiography plus stenting for PAD) with no procedure-related complications. Lung cancer (both non-small and small cell) was the most prevalent site. Single agent ICI was delivered in 10/40 cases (mainly atezolizumab), while combination with chemotherapy was recorded in 24/40 (pembrolizumab and atezolizumab), with TKIs in 4/40 (mainly nivolumab) and with bevacizumab in 2 cases. ICIs were mainly delivered as first-line treatment with a median treatment time of 9[range 6-16]months. Prevalent cardiovascular risk factors were smoking (72% active and former), hypertension (64%), lipids disorders (38%) and diabetes (16%).

Immunotherapy was resumed in all cases but 6 after a median of 1.5 [range 1-2]months and no new ASCVD episodes were recorded with a median follow-up of 14[range 6-20]months. In 5/6 patients ICIs were not restarted due to oncologist decision based on long-term disease control. Immunotherapy was permanently stopped due to the supposed high risk of CV toxicity in 1 case only.

Restarting immunotherapy after an acute event related to ASCVD does not seem to raise the risk of subsequent acute episodes. These preliminary results warrant prospective confirmation.