Acute vascular events as a possibly related adverse event of immunotherapy: a single-institute retrospective study

Bar, Jair; Markel, Gal; Gottfried, Teodor; Percik, Ruth; Leibowitz-Amit, Raya; Berger, Raanan; Golan, Talia; Daher, Sameh; Taliansky, Alisa; Dudnik, Elizabeth; Shulman, Katerina; Urban, Damien; Onn, Amir

doi:10.1016/j.ejca.2019.06.021

Cited by 83 publications

(100 citation statements)

References 35 publications

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“…7 In addition, Bar and colleagues retrospectively identified the occurrence of acute vascular events in 1215 ICI-treated patients with non-small cell lung cancer. 5 Approximately 1% of the patients in this cohort developed a myocardial infarction or stroke within the first 6 months after initiation of ICI therapy, suggesting that ICI-related vascular events resulted from effects on existing atherosclerotic plaques rather than on de novo lesion formation. 5 Although the optimal duration of ICI therapy is uncertain, these clinical observations suggest that even short-term ICI treatment may provoke atherosclerotic cardiovascular disease.…”

Section: Introductionmentioning

confidence: 89%

“…5 Approximately 1% of the patients in this cohort developed a myocardial infarction or stroke within the first 6 months after initiation of ICI therapy, suggesting that ICI-related vascular events resulted from effects on existing atherosclerotic plaques rather than on de novo lesion formation. 5 Although the optimal duration of ICI therapy is uncertain, these clinical observations suggest that even short-term ICI treatment may provoke atherosclerotic cardiovascular disease. Whether a longer duration of treatment further increases the risk for these adverse effects is currently not known.…”

Section: Introductionmentioning

confidence: 89%

“…5 Third, the occurrence of acute vascular events in ICI-treated patients significantly reduced the overall survival of these patients and 25.8% of the patients died within 4 weeks after the event, suggesting that prevention of these adverse atherosclerosis-related cardiovascular events improves the prognosis and qualityof-life of ICI-treated patients. 5 Another important point is the potential interaction between cardiovascular risk management and ICI therapy. For example, simvastatin, a β-hydroxy β-methylglutaryl-CoA (HMG-CoA) reductase inhibitor that is commonly used for the treatment of dyslipidemia, improved the efficacy of anti-PD1 therapy in experimental tumor models by directly enhancing anti-tumor T cell responses, suggesting that conventional cardiovascular drugs may affect the efficacy of ICI therapy, an important concept that warrants further investigation.…”

Section: Introductionmentioning

confidence: 93%

“…First, the majority of ICI-treated patients who developed acute vascular complications had at least two conventional cardiovascular risk factors, such as dyslipidemia, hypertension, obesity, a history of smoking or a previous cardiovascular event. 5 Second, atherosclerosis-related adverse events appear not to be correlated with the occurrence of other IRAE. 5 Third, the occurrence of acute vascular events in ICI-treated patients significantly reduced the overall survival of these patients and 25.8% of the patients died within 4 weeks after the event, suggesting that prevention of these adverse atherosclerosis-related cardiovascular events improves the prognosis and qualityof-life of ICI-treated patients.…”

Section: Introductionmentioning

confidence: 95%

“…5 Second, atherosclerosis-related adverse events appear not to be correlated with the occurrence of other IRAE. 5 Third, the occurrence of acute vascular events in ICI-treated patients significantly reduced the overall survival of these patients and 25.8% of the patients died within 4 weeks after the event, suggesting that prevention of these adverse atherosclerosis-related cardiovascular events improves the prognosis and qualityof-life of ICI-treated patients. 5 Another important point is the potential interaction between cardiovascular risk management and ICI therapy.…”

Section: Introductionmentioning

confidence: 95%

See 4 more Smart Citations

Cancer patients receiving immune checkpoint inhibitor therapy are at an increased risk for atherosclerotic cardiovascular disease

Lutgens

Seijkens

2020

J Immunother Cancer

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The widespread clinical use of immune checkpoint inhibitors (ICI) has increased our knowledge on their adverse effects on chronic inflammatory diseases. Atherosclerosis, a low-grade lipid-driven inflammatory disease of the larger arteries, is commonly present in cancer patients. A major concern is the adverse effect of ICI on atherosclerosis-related cardiovascular disease, resulting in cardiovascular events, such as myocardial infarction or ischaemic stroke. The effects of ICI on atherosclerosis in cancer patients are incompletely understood, but it is well known that immune checkpoint proteins orchestrate the inflammatory response underlying atherogenesis. This paper addresses the hypothesis that ICI therapy puts cancer patients at an increased risk for atherosclerosis-related cardiovascular disease, that might only become apparent years after ICI therapy. Until clinical and experimental studies have addressed this hypothesis, optimal cardiovascular risk management in ICI-treated patients is opportune to reduce the occurrence of cardiovascular disease in cancer patients and long-term cancer survivors.

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Section: Introductionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 95%

See 3 more Smart Citations

Cancer patients receiving immune checkpoint inhibitor therapy are at an increased risk for atherosclerotic cardiovascular disease

Lutgens

Seijkens

2020

J Immunother Cancer

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Venous thromboembolism risk in cancer patients receiving first‐line immune checkpoint inhibitor versus chemotherapy

May

et al. 2023

American J Hematol

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It remains unclear if immune checkpoint inhibitor (ICI) therapy is associated with higher rate of venous thromboembolism (VTE) compared with cytotoxic chemotherapy (chemo) in patients with comparable cancer type, staging, and comorbidities. Using the national Veterans Affairs healthcare system database from 2016 to 2021, we performed a propensity score (PS)‐weighted retrospective cohort study to compare the incidence of VTE in patients with selected stage III/IV cancer receiving first‐line ICI versus chemo. The PS model utilized overlap weights to balance age, sex, race, treatment year, VTE history, paralysis/immobilization, prolonged hospitalization, cancer type, staging, time between diagnosis and treatment, and National Cancer Institute comorbidity index. Weighted Cox regressions with robust standard error were used to assess the hazard ratio (HR) and 95% confidence interval (CI). We found that among comparable advanced cancers, first‐line ICI (n = 1823) and first‐line chemo (n = 6345) had similar rates of VTE (8.49% for ICI and 8.36% for chemo at 6 months). The weighted HR was 1.06 (95% CI 0.88–1.26) for ICI versus chemo. In a subgroup analysis restricted to lung cancers, first‐line ICI/chemo (n = 828), ICI monotherapy (n = 428), and chemo monotherapy (n = 4371) had similar rates of VTE (9.60% for ICI/chemo, 10.04% for ICI, and 8.91% for chemo at 6 months). The weighted HR was 1.05 (95% CI 0.77–1.42) for ICI versus chemo, and 1.08 (95% CI 0.83–1.42) for ICI/chemo versus chemo. In conclusion, ICI as a systemic therapy has a similarly elevated risk as cytotoxic chemo for VTE occurrence in cancer patients. This finding can inform future prospective studies exploring thromboprophylaxis strategies.

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Causal relationship between 14 site‐specific cancers and venous thromboembolism

et al. 2022

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Background It has been observed that cancer and venous thromboembolism (VTE) are associated, but anticancer therapy may violate the causality. Therefore, this study aimed to elucidate the causal relationship of various cancers to VTE using Mendelian randomization (MR). Methods Three MR methods were used to estimate causal effects: Inverse variance weighted (IVW), MR‐Egger and weighted median. Sensitivity analyses included Cochran's Q‐test, MR‐Egger intercept test and MR‐PRESSO. Gene ontology enrichment analysis was performed to elucidate the underlying mechanisms of VTE development in cancer patients. Results The primary IVW approach showed that non‐Hodgkin's lymphoma (NHL) might increase the risk of VTE (odds ratio [OR]: 1.20, 95% confidence interval [95% CI]: 1.00–1.44, p = 0.045), while melanoma possibly reduced the risk of VTE (OR: 0.89, 95% CI: 0.82–0.97, p = 0.006), although there was no significance after adjustment for multiple testing. No association was observed between VTE risk and other site‐specific cancers. Gene ontology enrichment analysis revealed that vitamin D played an important role in the development of VTE in cancer patients. Conclusions Our findings suggested that genetically predicted NHL was associated with higher VTE risk, whereas melanoma had lower VTE risk compared with other site‐specific cancers. Moreover, this study suggested that anticancer therapy and increased extensive examination might play a more important role in VTE development than the nature of cancer.

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Acute vascular events as a possibly related adverse event of immunotherapy: a single-institute retrospective study

Cited by 83 publications

References 35 publications

Cancer patients receiving immune checkpoint inhibitor therapy are at an increased risk for atherosclerotic cardiovascular disease

Cancer patients receiving immune checkpoint inhibitor therapy are at an increased risk for atherosclerotic cardiovascular disease

Venous thromboembolism risk in cancer patients receiving first‐line immune checkpoint inhibitor versus chemotherapy

Causal relationship between 14 site‐specific cancers and venous thromboembolism

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