Dataset Information

Risk Factors, Incidence, and Prognosis of Thromboembolism in Cancer Patients Treated With Immune Checkpoint Inhibitors.

ABSTRACT: In recent years, immune checkpoint inhibitors (ICIs) have become the standard treatment option for tumors. With the widespread application of ICIs, immune-related adverse events (irAEs) have gradually attracted the attention of researchers. Owing to the characteristics of ICIs, irAEs can affect each organ of the human body. Thromboembolism is uncommon in cancer patients receiving ICIs, but it may affect their survival. Most thromboembolic events do not cause serious effects after early prediction and treatment, but life-threatening toxic reactions are also observed. This condition should not be ignored because of vague and atypical symptoms, which make early diagnosis more challenging. This article focuses on the high-risk factors, underlying mechanisms, incidence, and prognosis of thromboembolism in patients using ICIs and briefly describes the intervention and treatment measures. This information would allow patients to effectively manage the side effects of thromboembolism during Immune checkpoint inhibitors treatment, ensuring the efficacy of ICIs and reducing mortality.

SUBMITTER: Zou XL

PROVIDER: S-EPMC8606686 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Risk Factors, Incidence, and Prognosis of Thromboembolism in Cancer Patients Treated With Immune Checkpoint Inhibitors.

Zou Xue-Lin XL Chen Wei-Yong WY Zhang Guang-Yan GY Ke Hua H Yang Qiu-Hong QH Li Xiao-Bo XB

Frontiers in pharmacology 20211108

In recent years, immune checkpoint inhibitors (ICIs) have become the standard treatment option for tumors. With the widespread application of ICIs, immune-related adverse events (irAEs) have gradually attracted the attention of researchers. Owing to the characteristics of ICIs, irAEs can affect each organ of the human body. Thromboembolism is uncommon in cancer patients receiving ICIs, but it may affect their survival. Most thromboembolic events do not cause serious effects after early predictio ...[more]

PMID: 34819857

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Project description:BackgroundThe incidence and risk factors of acute kidney injury (AKI) in patients with malignancies receiving immune checkpoint inhibitors (ICIs) are being extensively reported with their widespread application.ObjectiveThis study aimed to quantify the incidence and identify risk factors of AKI in cancer patients treated with ICIs.MethodsWe searched the electronic databases of PubMed/Medline, Web of Science, Cochrane and Embase before 1 February 2023 on the incidence and risk factors of AKI in patients receiving ICIs and registered the protocol in PROSPERO (CRD42023391939). A random-effect meta-analysis was performed to quantify the pooled incidence estimate of AKI, identify risk factors with pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) and investigate the median latency period of ICI-AKI in patients treated with ICIs. Assessment of study quality, meta-regression, and sensitivity and publication bias analyses were conducted.ResultsIn total, 27 studies consisting of 24048 participants were included in this systematic review and meta-analysis. The overall pooled incidence of AKI secondary to ICIs was 5.7% (95% CI: 3.7%-8.2%). Significant risk factors were older age (OR: 1.01, 95% CI: 1.00-1.03), preexisting chronic kidney disease (CKD) (OR: 2.90, 95% CI: 1.65-5.11), ipilimumab (OR: 2.66, 95% CI: 1.42-4.98), combination of ICIs (OR: 2.45, 95% CI: 1.40-4.31), extrarenal immune-related adverse events (irAEs) (OR: 2.34, 95% CI: 1.53-3.59), and proton pump inhibitor (PPI) (OR: 2.23, 95% CI: 1.88-2.64), nonsteroidal anti-inflammatory drug (NSAID) (OR: 2.61, 95% CI: 1.90-3.57), fluindione (OR: 6.48, 95% CI: 2.72-15.46), diuretic (OR: 1.78, 95% CI: 1.32-2.40) and angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) (pooled OR: 1.76, 95% CI: 1.15-2.68) use. Median time from ICIs initiation to AKI was 108.07 days. Sensitivity and publication bias analyses indicated robust results for this study.ConclusionThe occurrence of AKI following ICIs was not uncommon, with an incidence of 5.7% and a median time interval of 108.07 days after ICIs initiation. Older age, preexisting chronic kidney disease (CKD), ipilimumab, combined use of ICIs, extrarenal irAEs, and PPI, NSAID, fluindione, diuretics and ACEI/ARB use are risk factors for AKI in patients receiving ICIs.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023391939.

Project description:Background and objectives: Immune checkpoint inhibitor use in oncology is increasing rapidly. We sought to determine the frequency, severity, cause, and predictors of AKI in a real-world population receiving checkpoint inhibitors.Design, setting, participants, & measurements: We included all patients who received checkpoint inhibitor therapy from May 2011 to December 2016 at Massachusetts General Hospital. Baseline serum creatinine, averaged 6 months before checkpoint inhibitor start date, was compared with all subsequent creatinine values within 12 months of starting therapy. AKI was defined by Kidney Disease: Improving Global Outcomes criteria for fold changes in creatinine from baseline. Sustained AKI events lasted at least 3 days and was our primary outcome. The cause of sustained AKI was determined by chart review. Cumulative incidence and subdistribution hazard models were used to assess the relationship between baseline demographics, comorbidities, and medications, and sustained AKI and potential checkpoint inhibitor-related AKI.Results: We included 1016 patients in the analysis. Average age was 63 (SD 13) years, 61% were men, and 91% were white. Mean baseline creatinine was 0.9 mg/dl (SD 0.4 mg/dl), and 169 (17%) had CKD (eGFR<60 ml/min per 1.73 m2) at baseline. A total of 169 patients (17%) experienced AKI, defined by an increase in creatinine at least 1.5 times the baseline within 12 months; 82 patients (8%) experienced sustained AKI and 30 patients (3%) had potential checkpoint inhibitor-related AKI. The first episode of sustained AKI occurred, on average, 106 days (SD 85) after checkpoint inhibitor initiation. Sixteen (2%) patients experienced stage 3 sustained AKI and four patients required dialysis. Proton pump inhibitor use at baseline was associated with sustained AKI.Conclusions: AKI is common in patients receiving checkpoint inhibitor therapy. The causes of sustained AKI in this population are heterogenous and merit thorough evaluation. The role of PPI and other nephritis-inducing drugs in the development of sustained AKI needs to be better defined.

Project description:With the development and introduction of immune checkpoint inhibitors (ICIs) in cancer patients, immune-related side effects have increasingly attracted attention. However, the risks of immune-related renal toxicity are poorly characterized. In this study, we performed a network meta-analysis (NMA) of ICI-related randomized clinical trials (RCTs) to elucidate the comparative risk of acute kidney injury (AKI) in cancer patients receiving different ICIs. We also sought to identify other factors potentially affecting the risk of AKI. PubMed and EMBASE were searched for peer-reviewed trial reports published between January 2000 and May 2021. Eligible studies were RCTs studying ICIs in cancer patients and reporting AKI data. We performed a frequentist NMA to evaluate the risk ratios for grade 1-5 and grade 3-5 AKI between the treatment groups. We also assessed the absolute incidence of AKI in the ICI-containing arm using traditional direct meta-analysis. Once significant heterogeneity was detected in a traditional direct meta-analysis, multivariable meta-regression analysis was applied to identify factors that significantly affected the absolute incidence of AKI. A total of 85 RCTs were included in this study. In the NMA for the risk of grade 1-5 and 3-5 AKI, ipilimumab showed a significantly higher risk than avelumab and durvalumab, whereas 1 mg/kg nivolumab plus 3 mg/kg ipilimumab (N1I3) showed a significantly higher risk than other groups. In terms of treatment ranking, durvalumab ± low-dose tremelimumab and avelumab were consistently among the top three safest treatments for grade 1-5 or 3-5 AKI, whereas N1I3, ipilimumab and tremelimumab were consistently among the top three treatments with the highest risk for grade 1-5 or 3-5 AKI. Compared with other cancers, renal cell carcinoma and urothelial carcinoma showed a significantly higher risk of AKI. The incidence of AKI was significantly higher with ICI+chemotherapy than with ICI monotherapy. In this NMA involving large-scale up-to-date ICI trials, we demonstrated the comparative safety of existing ICI drugs for grade 1-5 and grade 3-5 AKI. Based on data from the ICI arms of these trials, we also revealed several potential risk factors for immune-related AKI, including tumor type and treatment paradigm.

Dataset Information

Risk Factors, Incidence, and Prognosis of Thromboembolism in Cancer Patients Treated With Immune Checkpoint Inhibitors.

Publications

Risk Factors, Incidence, and Prognosis of Thromboembolism in Cancer Patients Treated With Immune Checkpoint Inhibitors.

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