Checkpoint Inhibitors for Lung Cancer Linked to Pulmonary Embolism

BOSTON — Patients with metastatic lung cancer who were treated with immune checkpoint inhibitors (ICIs) had higher odds of developing a pulmonary embolism, according to a retrospective cohort study.

Among propensity-matched cohorts, 17% of patients with metastatic lung cancer who received ICIs developed a pulmonary embolism within 1 year of beginning treatment, compared with 14.6% of those who did not receive ICIs (OR 1.2, 95% CI 1.1-1.4, P=0.033), reported Cosmo Fowler, MD, of Emory University School of Medicine in Atlanta, at the CHEST 2024 annual meeting, hosted by the American College of Chest Physicians.

“Clinicians caring for patients with metastatic lung cancer treated with ICIs should be wary of signs and symptoms of thromboembolism, as these patients are at an even higher risk of thromboembolism than the baseline risk excess of metastatic cancer,” Fowler told attendees.

Investigators looked at the 1-year incidence of several venous and arterial thromboembolic events in this population, including deep vein thrombosis (DVT), myocardial infarction (MI), and cerebrovascular accidents (CVA).

In the propensity-matched cohorts, they found no significant difference between patients who received an ICI and those who did not for DVT or MI. Of note, however, ICIs appeared to be associated with lower odds of CVAs (10.4% vs 12.7%; OR 0.8, 95% CI 0.7-0.9, P=0.026).

Interestingly, the researchers found that PD-1 inhibitor recipients had significantly higher rates of pulmonary embolism than PD-L1 inhibitor recipients (20.3% vs 14.3%; OR 1.5, 95% CI 1.1-2.2, P=0.018). Otherwise, the two groups had comparable rates of DVT, MI, and CVA.

ICIs have revolutionized treatment of metastatic lung cancer and other cancers over the last 8 or 9 years, Fowler commented. However, their immunomodulatory mode of action that results in upregulation of T-cell activity essentially creates “an acquired autoimmune state with toxicities affecting any organ system in the body,” including the cardiovascular system. As more individuals are prescribed these medications, postmarketing reports of adverse events have increased, he noted.

“Are there any algorithms to predict which patients are going to have these [side effects]?” asked session moderator Sikander Zulqarnain, MD, MHA, of NYC Health and Hospitals/Kings County in Brooklyn. “At the end of the day, we have to figure out what to do with these patients.”

“At this moment … I couldn’t name a well-validated instrument to assess for these,” Fowler said. “As we move into a more data-rich future, the ability to generate models that predict the incidence of these effects will become easier and easier.”

“I’m definitely curious about the higher incidence [of pulmonary embolism] with anti-PD-1,” moderator Sisir Akkineni, MD, of the University of South Florida in Tampa, commented.

So far, there don’t appear to be any good explanations for this finding, Fowler replied, noting that as more postmarketing data accumulate, “we’ll have a better understanding and can make sure our patients get the safest ICI.”

Researchers used data from the large global TriNetX Research Network, identifying over 10,500 patients with metastatic lung cancer diagnosed from 2014 to 2023. Of these 1,630 received PD-1 inhibitors and no other type of ICI and 434 received at least one PD-L1 inhibitor. Propensity score matching accounted for 19 different demographic and comorbidity variables.

PD-1 inhibitors included cemiplimab (Libtayo), nivolumab (Opdivo), and pembrolizumab (Keytruda). Anti-PD-L1 inhibitors included atezolizumab (Tecentriq) and durvalumab (Imfinzi).

Before propensity score matching, all outcome events were more frequent among ICI recipients compared with those who did not receive them: DVT (20% vs 13.1%, OR 1.7), pulmonary embolism (17.7% vs 10.8%, OR 1.3), MI (11.6% vs 6.5%, OR 1.9), and CVA (10.9% vs 8.3%, OR 1.3; P

The study was subject to several limitations, including lack of individual patient chart data and data related to histology and previous lines of therapy.

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