Risk of Gastrointestinal Adverse Events in Cancer Patients Treated With Immune Checkpoint Inhibitor Plus Chemotherapy: A Systematic Review and Meta-Analysis

Abstract Background The association between prior exposure to immune checkpoint inhibitor (ICI) and outcomes of cancer patients with coronavirus disease 2019 (COVID-19) infection has yet to be systematically evaluated. As the current evidence remains equivocal, this meta-analysis aims to investigate the effects of ICI treatment on COVID-19 prognosis, including mortality, severity, and hospitalization.Methods Eligible studies published up to 14 September 2020 were included and assessed for risk of bias using the Quality in Prognosis Studies tool. A random-effects meta-analysis was conducted to estimate the pooled effect size along with 95% confidence intervals (CIs). The quality of body evidence was evaluated using the modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.Results Six studies involving a total of 1647 COVID-19-infected cancer patients were included in the systematic review. We discovered that prior ICI exposure was not associated with COVID-19 mortality (odds ratio [OR] 0.93 [95% CI: 0.37-2.36]; I2=30%), severity (OR 1.15 [95% CI: 0.40-3.28]; I2=0%), and hospitalization (OR 1.35 [95% CI: 0.64-2.87]; I2=51%). However, we discovered that prior exposure to chemoimmunotherapy predicted COVID-19 severity (OR 8.19 [95% CI: 2.67-25.08]; I2=0%), albeit with small sample size. GRADE assessments resulted in moderate-quality evidence for mortality, while the other outcomes yielded very low-to-low-quality evidenceConclusion Our findings indicated that ICI treatment should not be adjourned nor terminated during the current pandemic. Rather, COVID-19 vigilance should be increased, especially in patients receiving chemoimmunotherapy. Further studies with larger ICI cohorts are required to confirm our findingsTrial registration number: This project has been prospectively registered at PROSPERO (registration ID: CRD42020202142) on 4 August 2020.

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Association Between Sex and Immune-Related Adverse Events During Immune Checkpoint Inhibitor Therapy

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djab035 ◽

2021 ◽

Author(s):

Ying Jing ◽

Yongchang Zhang ◽

Jing Wang ◽

Kunyan Li ◽

Xue Chen ◽

...

Keyword(s):

Logistic Regression ◽

Adverse Events ◽

Cancer Patients ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Meta Analysis ◽

Omics Data ◽

Significant Difference ◽

Checkpoint Inhibitor Therapy

Abstract Background Accumulated evidence supports the existence of sex-associated differences in immune systems. Understanding the role of sex in immune-related adverse events (irAEs) is important for management of irAE in patients receiving immunotherapy. Methods We performed meta-analysis on published clinical study data and multivariable logistic regression on pharmacovigilance data and applied a propensity algorithm to The Cancer Genome Atlas (TCGA) omics data. We further validated our observations in two independent in-house cohorts of 179 and 767 cancer patients treated with immune checkpoint inhibitors. Results A meta-analysis using 13 clinical studies that reported on 1,096 female patients (36.8%, 95% confidence interval [CI] = 35.0%-38.5%) and 1,886 male patients (63.2%, 95% CI = 61.5%-65.0%) demonstrated no statistically significant irAE risk difference between the sexes (odds ratio [OR] = 1.19; 95% CI = 0.91-1.54; 2-sided P = 0.21). Multivariable logistic regression analysis of 12,225 patients from FAERS and 10,979 patients from VigiBase showed no statistically significant difference in irAEs by sex. A propensity score algorithm used on multi-omics data for 6,019 patients from TCGA found no statistically significant difference by sex for irAE-related factors/pathways. The retrospective analysis of two in-house patient cohorts validated these results (OR = 1.55, 95% CI = 0.98-2.47; FDR = 0.13, for cohort 1; OR = 1.16, 95%CI = 0.86-1.57; FDR = 0.39, for cohort 2). Conclusion We observed minimal sex-associated differences in irAEs among cancer patients who received immune checkpoint inhibitor therapy. It may be unnecessary to consider gender effects for irAE management in clinical practice.

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