An overview of the toxicities of checkpoint inhibitors in older patients with cancer

Alkharabsheh, Omar; Kannarkatt, Paul; Kannarkatt, Joseph; Karapetyan, Lilit; Laird-Fick, Heather; Al-Janadi, Anas

doi:10.1016/j.jgo.2018.02.002

Cited by 20 publications

(10 citation statements)

References 54 publications

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“…Forty-six percent of the patients were age ≥ 65 years and 16% were age ≥ 75 years. No overall differences in safety were observed between older and younger patients [33, 34]. This was recently confirmed in an update that was presented at the European Lung Cancer Congress 2019, in which it was shown that there was no difference in irAEs between patients aged < 75 and > 75 years [35].…”

Section: Immune-related Adverse Events In Older Patientsmentioning

confidence: 84%

“…It must be noted that the impact of irAEs in elderly patients may be greater than in younger patients, owing to age-related comorbidities and reduced functional reserve. For example, thyroiditis can result in either hypothyroidism or hyperthyroidism, which might worsen the symptoms of an undiagnosed neurocognitive disorder [33]. Interactions of adverse events and comorbidities may be problematic.…”

Section: Discussionmentioning

confidence: 99%

“…In total, 1359 patients were treated with nivolumab, of whom 39% were aged ≥ 65 years and 9% were aged ≥ 75 years. No overall differences in safety were observed between older and younger patients [33, 36]. Spigel et al presented a pooled analysis of 520 patients aged ≥ 70 years and 108 patients with a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 2, receiving nivolumab for metastatic NSCLC in the Checkmate 153 trial.…”

Section: Immune-related Adverse Events In Older Patientsmentioning

confidence: 99%

“…The data show more reported grade 3–5 adverse events in patients aged ≥ 70 years and a trend towards a higher incidence of irAEs requiring treatment with immune-modulating medication in this group. The indications for immune-modulating medication were mostly rash or colitis [33, 38].…”

Section: Immune-related Adverse Events In Older Patientsmentioning

confidence: 99%

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Efficacy and Adverse Events of Immunotherapy with Checkpoint Inhibitors in Older Patients with Cancer

et al. 2019

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The number of older patients with cancer is increasing as a result of the ageing of Western societies. Immune checkpoint inhibitors have improved cancer treatment and are associated with lower rates of treatment-related toxicity compared with chemotherapy in the general population. Nonetheless, immune checkpoint inhibitors have potentially serious immune-related adverse events, which might have a greater impact on older and more vulnerable patients and potentially influence treatment efficacy and quality of life. Previous clinical trials have shown no major increase in immune-related adverse events; however, older patients are underrepresented and relatively healthy in these trials. Observational studies suggest that older and more vulnerable patients may be at a higher risk of immune-related adverse events and early treatment discontinuation. Geriatric assessment could help identify older patients who will benefit from immune checkpoint inhibitors.

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Section: Immune-related Adverse Events In Older Patientsmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Immune-related Adverse Events In Older Patientsmentioning

confidence: 99%

Section: Immune-related Adverse Events In Older Patientsmentioning

confidence: 99%

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Efficacy and Adverse Events of Immunotherapy with Checkpoint Inhibitors in Older Patients with Cancer

et al. 2019

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“…Whether patients who are treated with ipilimumab have an increased risk of developing atherosclerotic cardiovascular disease is currently unknown, as atherosclerosis develops gradually over years or decades and immune checkpoint inhibitors have been implemented in the clinic only in the past decade [31]. Moreover, the elderly, who often have subclinical atherosclerosis, and patients with a history of cardiovascular disease were excluded from most of the clinical trials that investigated ipilimumab in cancer patients [32]. Nevertheless, a meta-analysis of 22 trials that investigated the efficacy of another immune checkpoint inhibitor targeting the co-inhibitory PD1-PDL1 dyad in patients with lung cancer demonstrated that atherosclerotic cardiovascular disease occurred in 3% of the patients [33].…”

Section: Discussionmentioning

confidence: 99%

Antibody-Mediated Inhibition of CTLA4 Aggravates Atherosclerotic Plaque Inflammation and Progression in Hyperlipidemic Mice

Poels

Leent

Reiche

et al. 2020

Cells

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T cell-driven inflammation plays a critical role in the initiation and progression of atherosclerosis. The co-inhibitory protein Cytotoxic T-Lymphocyte Associated protein (CTLA) 4 is an important negative regulator of T cell activation. Here, we studied the effects of the antibody-mediated inhibition of CTLA4 on experimental atherosclerosis by treating 6–8-week-old Ldlr−/− mice, fed a 0.15% cholesterol diet for six weeks, biweekly with 200 μg of CTLA4 antibodies or isotype control for six weeks. 18F-fluorodeoxyglucose Positron Emission Tomography—Computed Tomography showed no effect of the CTLA4 inhibition of activity in the aorta, spleen, and bone marrow, indicating that monocyte/macrophage-driven inflammation was unaffected. Correspondingly, flow cytometry demonstrated that the antibody-mediated inhibition of CTLA4 did not affect the monocyte populations in the spleen. αCTLA4 treatment induced an activated T cell profile, characterized by a decrease in naïve CD44−CD62L+CD4+ T cells and an increase in CD44+CD62L− CD4+ and CD8+ T cells in the blood and lymphoid organs. Furthermore, αCTLA4 treatment induced endothelial activation, characterized by increased ICAM1 expression in the aortic endothelium. In the aortic arch, which mainly contained early atherosclerotic lesions at this time point, αCTLA4 treatment induced a 2.0-fold increase in the plaque area. These plaques had a more advanced morphological phenotype and an increased T cell/macrophage ratio, whereas the smooth muscle cell and collagen content decreased. In the aortic root, a site that contained more advanced plaques, αCTLA4 treatment increased the plaque T cell content. The short-term antibody-mediated inhibition of CTLA4 thus accelerated the progression of atherosclerosis by inducing a predominantly T cell-driven inflammation, and resulted in the formation of plaques with larger necrotic cores and less collagen. This indicates that existing therapies that are based on αCTLA4 antibodies may promote CVD development in patients.

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Immunotherapy

Decoster

Aspeslagh

2021

Encyclopedia of Gerontology and Population Aging

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An overview of the toxicities of checkpoint inhibitors in older patients with cancer

Cited by 20 publications

References 54 publications

Efficacy and Adverse Events of Immunotherapy with Checkpoint Inhibitors in Older Patients with Cancer

Efficacy and Adverse Events of Immunotherapy with Checkpoint Inhibitors in Older Patients with Cancer

Antibody-Mediated Inhibition of CTLA4 Aggravates Atherosclerotic Plaque Inflammation and Progression in Hyperlipidemic Mice

Immunotherapy

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