Immune Checkpoint Inhibitors and Cardiac Toxicity in Patients Treated for Non-Small Lung Cancer: A Review

Sławiński, Grzegorz; Wrona, Anna; Dąbrowska−Kugacka, Alicja; Raczak, Grzegorz; Lewicka, Ewa

doi:10.3390/ijms21197195

Cited by 59 publications

(56 citation statements)

References 97 publications

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“…Meanwhile, there is increasing concern regarding immunerelated adverse events (irAEs) of ICIs (12)(13)(14). The appearance of some irAEs have beenshown to be related to the efficacy of ICI agents in patients with NSCLC and melanoma (15,16), but this relationship has not been established in patients with SCLC.…”

Section: Introductionmentioning

confidence: 99%

Immune Check Point Inhibitors and Immune-Related Adverse Events in Small Cell Lung Cancer

Hou

Zhou

et al. 2021

Front. Oncol.

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Small cell lung cancer (SCLC) is a malignant solid tumor. In recent years, although immune check point inhibitors (ICIs) have achieved important advances in the treatment of SCLC, immune-related adverse events (irAEs) have occurred at the same time during the therapeutic period. Some irAEs lead to dose reduction or treatment rejection. The immune microenvironment of SCLC is complicated, therefore, understanding irAEs associated with ICIs is of great importance and necessity for the clinical management of SCLC. However, the lack of comprehensive understanding of irAEs in patients with SCLC remains remarkable. This review aims to provide an up-to-date overview of ICIs and their associated irAEs in patients with SCLC based on present clinical data.

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Section: Introductionmentioning

confidence: 99%

Immune Check Point Inhibitors and Immune-Related Adverse Events in Small Cell Lung Cancer

Hou

Zhou

et al. 2021

Front. Oncol.

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“…As a key immunoregulatory molecule, PD-L1 interacts with its immune checkpoint receptor PD-1 (programmed cell death protein 1), which is expressed on the surface of macrophages and activated T cells and B cells. The binding of PD-L1 to PD-1 enhances immunosuppression and avoids tumor-induced immune destruction by inhibiting the proliferation and survival of cytotoxic T cells and reducing cytokine production [23][24][25]. In NSCLC patients, positive PD-L1 expression is observed in 50% to 70% of cases [23].…”

Section: Introductionmentioning

confidence: 99%

“…The binding of PD-L1 to PD-1 enhances immunosuppression and avoids tumor-induced immune destruction by inhibiting the proliferation and survival of cytotoxic T cells and reducing cytokine production [23][24][25]. In NSCLC patients, positive PD-L1 expression is observed in 50% to 70% of cases [23]. Recently, expression of PD-L1 was reported to be associated with increased tumor proliferation and aggressiveness, as well as shorter survival times for patients with NSCLC [26].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, expression of PD-L1 was reported to be associated with increased tumor proliferation and aggressiveness, as well as shorter survival times for patients with NSCLC [26]. The evolvement of immune checkpoint inhibitors (ICI) based on PD-1 inhibition (e.g., nivolumab, pembrolizumab) and PD-L1 inhibition (durvalumab, atezolizumab, and avelumab) have significantly improved the survival rates and clinical outcomes in patients with metastatic NSCLC [23,27]. Moreover, in first-line and second-line settings, ICI monotherapy and dual therapy or a therapeutic approach in combination with chemotherapy has displayed an overall survival benefit compared to standard platinum-based regimens [23,[27][28][29].…”

Section: Introductionmentioning

confidence: 99%

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Clinicopathological and Prognostic Significance of Inhibitor of Apoptosis Protein (IAP) Family Members in Lung Cancer: A Meta-Analysis

Fung

Knoefel

Krieg

2021

Cancers

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Lung cancer is the most common cause of cancer-related death worldwide. Approximately 85% is non-small-cell and 15% is small-cell lung cancer. The inhibitor of apoptosis proteins (IAPs) represent a heterogeneous family of anti-apoptotic proteins, some members of which have been reported to correlate with clinical outcome in lung cancer. We screened PubMed, Web of Science, and Scopus for studies that investigated the prognostic value and clinicopathological features of IAPs in lung cancer. Forty-five eligible studies with 4428 patients assessed the expression of the IAPs survivin, XIAP, livin, and BRUCE. The pooled hazard ratio (HR) of 33 studies that analyzed overall survival (OS) revealed a positive correlation between survivin expression and poor prognosis. Seven studies displayed a strong association between survivin and disease recurrence. Two studies that assessed the expression of XIAP and livin, respectively, proved a significant relationship of these IAPs with poor OS. Meta-analyses of clinicopathological variables revealed a significant association between survivin and T stage, UICC stage, the presence of lymph node metastasis, and grade of differentiation. In conclusion, high expression of distinct IAPs significantly correlates with prognosis in lung cancer. Therefore, lung cancer patients might benefit from a targeted therapy against specific IAPs.

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“…Limited reports and researches supported a trend that there was a lower major adverse cardiac events rate with higher starting doses of immunosuppression (4). The dose of steroids should be gradually reduced after 3-5 days, tapering over one month and even longer in some severe cases (9). Both of our patients were treated with corticosteroids while the first patients received a higher dose of methylprednisolone and a slower course of dose reduction.…”

Section: Discussionmentioning

confidence: 90%

Myocarditis related to immune checkpoint inhibitors treatment: two case reports and literature review

Jia¹,

Liu²,

Shen³

et al. 2021

Ann Palliat Med

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Immune checkpoint inhibitors can cause immune-related toxicity in various systems, and myocarditis is the most serious life-threatening toxicity. This report introduces diagnosis and treatment of two cases which developed myocarditis after receiving PD-1 inhibitors therapy. The first case was a 77-yearold male with chordoma, who was treated by third-line sintilimab combined with anlotinib, and presented with symptoms of chest tightness, shortness of breath and upper eyelid ptosis three weeks later. He was diagnosed as immune-checkpoint-inhibitors-related myocarditis and myositis-myasthenia-gravis overlap syndrome based on his clinical symptoms, serum biomarkers, electrocardiogram, echocardiogram, and characteristic findings on cardiac 18F-FDG PET-MRI. Methylprednisolone was given 480 mg/d initially and was gradually reduced to 40 mg/d in 4 weeks, with the myocardial injury biomarkers declined in the same time. The second case was a 69-year-old female with advanced non-small cell lung cancer, who was treated by pemetrexed combined with bevacizumab and camrelizumab, and presented with palpitations 20 days later. She was diagnosed as immune-checkpoint-inhibitors-related myocarditis based on her clinical symptoms, serum biomarkers, electrocardiogram and echocardiogram. Methylprednisolone was given 240 mg/d initially and was gradually reduced to 40 mg/d with good response of myocardial injury biomarkers decline.However, the patient developed fatal myasthenia gravis afterwards, with little response to all treatments. These two cases revealed that, early detection and timely intervention, including discontinuation of immune checkpoint inhibitors and initiation of adequate steroid therapy, can reduce morbidity and mortality and improve prognosis.

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Immune Checkpoint Inhibitors and Cardiac Toxicity in Patients Treated for Non-Small Lung Cancer: A Review

Cited by 59 publications

References 97 publications

Immune Check Point Inhibitors and Immune-Related Adverse Events in Small Cell Lung Cancer

Immune Check Point Inhibitors and Immune-Related Adverse Events in Small Cell Lung Cancer

Clinicopathological and Prognostic Significance of Inhibitor of Apoptosis Protein (IAP) Family Members in Lung Cancer: A Meta-Analysis

Myocarditis related to immune checkpoint inhibitors treatment: two case reports and literature review

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