Risk of COVID-19 in Patients with Cancer Receiving Immune Checkpoint Inhibitors.
Ontology highlight
ABSTRACT: Objective
The aim of this study was to determine the rate of coronavirus disease-19 (COVID-19) among patients with cancer treated with immune checkpoint inhibitors (ICIs).Materials and methods
This was a retrospective study of 1,545 patients with cancer treated with ICIs between July 1, 2019, and February 29, 2020, and 20,418 age-, sex-, and cancer category-matched controls in a large referral hospital system. Confirmed COVID-19 case and mortality data were obtained with Massachusetts Department of Public Health from March 1 through June 19, 2020.Results
The mean age was 66.6 years, and 41.9% were female. There were 22 (1.4%) and 213 (1.0%) COVID-19 cases in the ICI and control groups, respectively. When adjusting for demographics, medical comorbidities, and local infection rates, ICIs did not increase COVID-19 susceptibility.Conclusion
ICIs did not increase the rate of COVID-19. This information may assist patients and their oncologists in decision-making surrounding cancer treatment during this pandemic.
SUBMITTER: Klebanov N
PROVIDER: S-EPMC8100539 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:To date, few data are available regarding Adverse events (AEs) in cancer patients who are vaccinated for coronavirus disease 2019 (COVID-19) while being actively treated with Immune-checkpoint inhibitors (ICIs). We aimed to assess the safety of COVID-19 vaccines approved in Germany. Specifically, we investigated the frequency of general side effects and immune-related AEs of COVID-19 vaccination. A triage survey was used to collect the following information for patients with metastatic skin cancer: vaccine type, date of receipt of each dose of vaccine, and self-reported side effects. Clinical data were retrieved from the patients' medical records. Of 130 patients with metastatic skin cancer, 89 patients were on immunotherapy and received COVID-19 vaccination. Of these 89 patients (median age: 64 years; 57 [64%] men), 89% had melanoma, and 71% received ICI therapy with a PD-1 antibody. Eighty-eight percent received an mRNA-based COVID-19 vaccination. The median follow-up time was 125 days after the first vaccination, and 84 days after the second. The most common observed side effects were mild to moderate pain at the injection site (40%), followed by fatigue (24%). Grade 3 irAEs were reported in eight patients, seven of whom were on nivolumab plus ipilimumab combination treatment. Of the 19 patients vaccinated within 72 h before/after ICI, five developed irAEs within 17 days (1-17 days). This small cohort study suggests that approved COVID-19 vaccinations are safe for use in cancer patients receiving ICIs. However, some precautions should be taken, especially regarding the timing of vaccination and ICI treatment.
| S-EPMC8695667 | biostudies-literature
Project description:BackgroundCancer patients are at a higher risk for developing influenza (flu)- related complications. It is unclear if the flu vaccine exacerbates immune events in patients treated with immune checkpoint inhibitors (ICIs).MethodsWe conducted an institutional review board-IRB-approved retrospective review of advanced cancer patients on ICIs who received the flu vaccine during three 3 consecutive seasons: 2014-2015, 2015-2016, and 2016-2017. The primary outcome assessed was any "new onset" immune-related adverse event (IRAE). A subset analysis of vaccinated patients newly treated with anti-programmed cell death protein 1 (PD-1) agents (nivolumab or pembrolizumab) was conducted to assess overall IRAE rates for comparison with published clinical trials.ResultsDuring the three 3 seasons, 370 patients met criteria for ICI and vaccination within ~ twoapproximately 2 months (65 days). The most common underlying cancers were lung (46%) and melanoma (19%); 61% of patients received an anti-PD-1 agent only. In the entire cohort, 20% experienced an IRAE (any grade); incidence of grade 3 or 4 toxicity was 8%. No grade 5 events occurred. In the subset of 170 patients newly treated with anti-PD-1 agents, the overall IRAE rate was 18% and, grade 3/4 events occurred in 7.6%. Influenza was diagnosed in 2 patients.ConclusionsNo increase in incidence or severity of IRAEs was detected in patients on ICIs who received the inactivated influenza vaccine within ~ approximately 2 months of ICI. For newly treated patients on anti-PDI-1 agents, IRAE rates were comparable to those from published clinical trials and did not vary with order of administration. Routine seasonal flu vaccination is encouraged in patients on ICIs.
| S-EPMC6938975 | biostudies-literature
Project description:BackgroundImmune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but are associated with immune-mediated diarrhea and colitis (IMDC). Clostridioides difficile infection (CDI) can cause infectious diarrhea with overlapping symptoms. Thus, we sought to elucidate the characteristics of CDI in patients treated with ICI, in the context of IMDC.MethodsWe conducted a retrospective, single-center study of adult cancer patients (N=421) with ICI exposure from 2015-2020 and a positive stool nucleic acid amplification test and/or enzyme immunoassay for CDI. Baseline characteristics, treatments, and outcomes were compared between patients with and without concurrent IMDC.ResultsForty-one eligible patients were included, 27 with concurrent IMDC and 14 without. Twenty-seven patients were taking programmed death-1 or its ligand inhibitors and 14 were taking cytotoxic T-lymphocyte-associated antigen 4 inhibitors. Patients with concurrent CDI and IMDC had a longer symptom duration (20 vs. 5 days, P=0.003) and a higher rate of grade 3-4 diarrhea (41% vs. 7%, P=0.033). Among patients with concurrent IMDC, preceding antibiotics (P=0.050) and proton pump inhibitors (PPI) (P=0.038) were used more frequently among individuals who developed CDI after immunosuppressant exposure. Thirty-eight patients received antibiotics for CDI, while 5 required fecal microbiota transplantation for concurrent CDI & IMDC.ConclusionsCDI is common in ICI-treated cancer patients, especially those with IMDC requiring immunosuppressants. Antibiotics did not alter the need for immunosuppressants in those with concurrent IMDC. Use of PPI and antibiotics while receiving immunosuppressants for IMDC was associated with a greater risk of CDI. Further large-scale studies are warranted to clarify the role of CDI, antibiotics and immunosuppression treatment in IMDC patients.
| S-EPMC9210781 | biostudies-literature
Project description:The clinical and immunologic implications of the SARS-CoV-2 pandemic for patients with cancer receiving systemic anticancer therapy have introduced a multitude of clinical challenges and academic controversies. This review summarizes the current evidence, discussion points, and recommendations regarding the use of immune checkpoint inhibitors (ICIs) in patients with cancer during the SARS-CoV-2 pandemic, with a focus on patients with melanoma and renal cell carcinoma (RCC). More specifically, we summarize the theoretical concepts and available objective data regarding the relationships between ICIs and the antiviral immune response, along with recommended clinical approaches to the management of melanoma and RCC patient cohorts receiving ICIs throughout the course of the COVID-19 pandemic. Additional insights regarding the use of ICIs in the setting of current and upcoming COVID-19 vaccines and broader implications toward future pandemics are also discussed.
| S-EPMC8288220 | biostudies-literature
Project description:BackgroundImmune evasion is a hallmark of cancer and is associated with resistance to PD-1/PD-L1 and CTLA-4 inhibitors. Several interactions between tumor and immune cells within the tumor microenvironment are effected through integrin signaling; however the latter has been underrecognized as a pathway that could have an impact on oncological outcomes after treatment with immune checkpoint inhibitors (ICIs). This study aimed to assess the clinical relevance of genomic alterations in the integrin signaling pathway in ICI-treated patients with advanced cancers.MethodsNext generation sequencing (NGS) data from tumor samples of patients with advanced cancers treated with ICIs (anti-PD-1/PD-L1, anti-CTLA4 or both) were queried from four independent publicly available cohorts for mutations and structural variations in 72 integrin signaling pathway genes (Gene Set: GOBP_CELL_ADHESION_MEDIATED_BY_INTEGRIN). The Kaplan Meier method was used to assess the association between mutated and unmutated genes with overall (OS) and progression-free survival (PFS). All results were reported at the 0.05 significance level.ResultsThe largest cohort included 1662 patients (discovery set) and comprised 350 non-small cell lung cancer (NSCLC), 321 melanoma, 214 bladder, 151 renal cell carcinoma (RCC), 138 head neck (HN), 126 esophageal/gastric (EG), 117 glioma, 110 colorectal (CRC), 90 cancer of unknown primary (CUP), and 45 breast cancer patients. ICI treatments included PD-1 or PD-L1 inhibitors (n=1256), anti-CTLA4 inhibitors (n=146) or both (n=260). 170 patients (10% of the entire cohort) harbored mutations in PIK3CG (6%), RET (3%), SYK (1.4%), LYN (1.4%), PTPN11 (1.3%), and CRKL (0.1%) genes. Presence of these mutations was more frequent in melanoma (18%), followed by CRC (14.5%), CUP (11%), and NSCLC (11%). Patients with mutated tumors experienced a significantly longer median OS (41 months) compared to those without alterations (16 months, log-rank P<0.001). The favorable prognostic value of PIK3CG, RET, SYK, LYN, PTPN11, and CRKL alterations was confirmed in three melanoma cohorts (validation set, n=212, P=0.024). Assessment of mutation status of these genes in a fourth cohort of NSCLC patients (n=75) revealed a predictive significance as well, with regard to PFS after treatment with ipilimumab and nivolumab combination (P=0.048).ConclusionMutations and/or structural variations in integrin signaling genes may have prognostic and predictive value in patients with metastatic malignancies who receive ICIs. Although confirmation in larger studies with concurrent investigation of underlying immunologic mechanisms is needed, these findings pose therapeutic implications for co-targeted approaches to overcome immune evasion and resistance.
| S-EPMC8661141 | biostudies-literature
Project description:BACKGROUND:Influenza vaccination (FV) is recommended for patients with cancer. Recent data suggested that the administration of the FV was associated with an increase in immune-related adverse events (irAEs) among patients on immune checkpoint inhibitors (ICIs). Myocarditis is an uncommon but serious complication of ICIs and may also result from infection with influenza. There are no data testing the relationship between FV and the development of myocarditis on ICIs. METHODS:Patients on ICIs who developed myocarditis (n?=?101) (cases) were compared to ICI-treated patients (n?=?201) without myocarditis (controls). A patient was defined as having the FV if they were administered the FV from 6?months prior to start of ICI to anytime during ICI therapy. Alternate thresholds for FV status were also tested. The primary comparison of interest was the rate of FV between cases and controls. Patients with myocarditis were followed for major adverse cardiac events (MACE), defined as the composite of cardiogenic shock, cardiac arrest, hemodynamically significant complete heart block and cardiovascular death. RESULTS:The FV was administered to 25% of the myocarditis cases compared to 40% of the non-myocarditis ICI-treated controls (p?=?0.01). Similar findings of lower rates of FV administration were noted among myocarditis cases when alternate thresholds were tested. Among the myocarditis cases, those who were vaccinated had 3-fold lower troponin levels when compared to unvaccinated cases (FV vs. No FV: 0.12 [0.02, 0.47] vs. 0.40 [0.11, 1.26] ng/ml, p?=?0.02). Within myocarditis cases, those administered the FV also had a lower rate of other irAEs when compared to unvaccinated cases (36 vs. 55% p?=?0.10) including lower rates of pneumonitis (12 vs. 36%, p?=?0.03). During follow-up (175 [IQR 89, 363] days), 47% of myocarditis cases experienced a MACE. Myocarditis cases who received the FV were at a lower risk of cumulative MACE when compared to unvaccinated cases (24 vs. 59%, p?=?0.002). CONCLUSION:The rate of FV among ICI-related myocarditis cases was lower than controls on ICIs who did not develop myocarditis. In those who developed myocarditis related to an ICI, there was less myocardial injury and a lower risk of MACE among those who were administered the FV.
| S-EPMC6387531 | biostudies-literature
Project description:The severe acute respiratory syndrome associated coronavirus?2 (SARS?CoV?2) poses a threat to human life worldwide. Since early March, 2020, coronavirus disease 2019 (COVID?19), characterized by an acute and often severe form of pneumonia, has been declared a pandemic. This has led to a boom in biomedical research studies at all stages of the pipeline, from the in vitro to the clinical phase. In line with this global effort, known drugs, currently used for the treatment of other pathologies, including antivirals, immunomodulating compounds and antibodies, are currently used off?label for the treatment of COVID?19, in association with the supportive standard care. Yet, no effective treatments have been identified. A new hope stems from medical oncology and relies on the use of immune?checkpoint inhibitors (ICIs). In particular, amongst the ICIs, antibodies able to block the programmed death?1 (PD?1)/PD ligand-1 (PD?L1) pathway have revealed a hidden potential. In fact, patients with severe and critical COVID?19, even prior to the appearance of acute respiratory distress syndrome, exhibit lymphocytopenia and suffer from T?cell exhaustion, which may lead to viral sepsis and an increased mortality rate. It has been observed that cancer patients, who usually are immunocompromised, may restore their anti?tumoral immune response when treated with ICIs. Moreover, viral-infected mice and humans, exhibit a T?cell exhaustion, which is also observed following SARS?CoV?2 infection. Importantly, when treated with anti?PD?1 and anti?PD?L1 antibodies, they restore their T?cell competence and efficiently counteract the viral infection. Based on these observations, four clinical trials are currently open, to examine the efficacy of anti?PD?1 antibody administration to both cancer and non?cancer individuals affected by COVID?19. The results may prove the hypothesis that restoring exhausted T?cells may be a winning strategy to beat SARS?CoV?2 infection.
| S-EPMC7864014 | biostudies-literature
Project description:IntroductionPreclinical studies have demonstrated the ability of radiation therapy (RT) to augment immune response and tumor control by immune checkpoint inhibitors (ICI). However, numerous clinical trials combining RT and ICI have yielded relatively disappointing results. To improve understanding of optimal use of these therapies, we assessed systemic immune effects of prior RT in patients receiving ICI.Methods and materialsPre- and post-ICI blood samples were collected from patients enrolled in a prospective immunotherapy biospecimen protocol. Mutiplex panels of 40 cytokines and 120 autoantibodies (Ab) were analyzed. We identified differences in these parameters according to receipt, timing, and type of prior RT. We calculated P values using the Pearson product-moment correlation coefficient and false discovery rate (FDR) using the Benjamini-Hochberg Procedure.ResultsAmong 277 total patients, 69 (25%) received RT in the 6 months prior to ICI initiation. Among RT-treated patients, 23 (33%) received stereotactic RT, and 33 (48%) received curative intent RT. There was no significant difference in demographics or type of immunotherapy between patients according to prior RT exposure. Baseline complement C8 Ab and MIP-1d/CCL15 were significantly higher among patients with prior RT. For MIP-1d/CCL15, only prior stereotactic RT was associated with significant differences.ConclusionsPrior RT is associated with few changes in systemic immune parameters in patients receiving ICI. The underlying mechanisms and optimal approach to harnessing the potential synergy of RT and ICI require further prospective clinical investigation.
| S-EPMC10265517 | biostudies-literature
Project description:BackgroundHyponatremia due to endocrinopathies such as adrenal insufficiency and hypothyroidism has been reported in patients receiving immune checkpoint inhibitors (ICIs). We determined the risk and predictors of hyponatremia and other electrolyte abnormalities in a 'real-world' sample of patients receiving ICIs to treat advanced malignancies.MethodsThis was a retrospective observational study of all patients who received ICIs from a single cancer center between 2011 and 2018. Patients were followed for 12 months after initiation of ICIs or until death. Common Terminology for Cancer Adverse Events version 5.0 criteria were used to grade the severity of hyponatremia and other electrolyte abnormalities. The predictors of severe (Grade 3 or 4) hyponatremia were determined using a multivariable logistic regression model. The etiology of Grade 3 or 4 hyponatremia was determined by chart review.ResultsA total of 2458 patients were included. Their average age was 64 years [standard deviation (SD) 13], 58% were male and 90% were white. In the first year after starting ICIs, 62% experienced hyponatremia (sodium <134 mEq/L) and 136 (6%) experienced severe hyponatremia (<124 mEq/L). Severe hyponatremia occurred on average 164 days (SD 100) after drug initiation. Only nine cases of severe hyponatremia were due to endocrinopathies (0.3% overall incidence). Risk factors for severe hyponatremia included ipilimumab (a cytotoxic T lymphocyte antigen-4 inhibitor) use, diuretic use and non-White race. Other severe electrolyte abnormalities were also commonly observed: severe hypokalemia (potassium <3.0 mEq/L) occurred in 6%, severe hyperkalemia (potassium ≥6.1 mEq/L) occurred in 0.6%, severe hypophosphatemia (phosphorus <2 mg/dL) occurred in 17% and severe hypocalcemia (corrected calcium <7.0 mg/dL) occurred in 0.2%.ConclusionsHyponatremia is common in cancer patients receiving ICIs. However, endocrinopathies are an uncommon cause of severe hyponatremia.
| S-EPMC8643613 | biostudies-literature
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.
| S-EPMC6895474 | biostudies-literature