Safety of Inactivated Influenza Vaccine in Cancer Patients Receiving Immune Checkpoint Inhibitors.
Ontology highlight
ABSTRACT: Background
Cancer 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).Methods
We 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.Results
During 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.Conclusions
No 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.
SUBMITTER: Chong CR
PROVIDER: S-EPMC6938975 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundInfluenza 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.MethodsPatients 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.ResultsThe 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).ConclusionThe 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 potential increased risk of immune-related adverse events (irAEs) post-influenza vaccine is a concern in patients receiving immune checkpoint inhibitors (ICI). We conducted a systematic review with meta-analysis of studies reporting the effects of influenza vaccination in patients with cancer during ICI treatment. We searched five electronic databases until 01/2022. Two authors independently selected studies, appraised their quality, and collected data. The primary outcome was the determination of pooled irAE rates. Secondary outcomes included determination of immunogenicity and influenza infection rates and cancer-related outcomes. Nineteen studies (26 publications, n = 4705) were included; 89.5% were observational. Vaccinated patients reported slighter lower rates of irAEs compared to unvaccinated patients (32% versus 41%, respectively). Seroprotection for influenza type A was 78%-79%, and for type B was 75%. Influenza and irAE-related death rates were similar between groups. The pooled proportion of participants reporting a laboratory-confirmed infection was 2% (95% CI 0% to 6%), and influenza-like illness was 14% (95% CI 2% to 32%). No differences were reported on the rates of laboratory-confirmed infection between vaccinated and unvaccinated patients. Longer progression-free and overall survival was also observed in vaccinated compared with unvaccinated patients. Current evidence suggests that influenza vaccination is safe in patients receiving ICIs, does not increase the risk of irAEs, and may improve survival.
| S-EPMC9412390 | biostudies-literature
Project description:BackgroundImmune checkpoint inhibitors (ICIs), used for the treatment of solid and hematologic malignancies, come with the risk of immune-related adverse events (irAEs). Opportunistic infections (e.g., cytomegalovirus [CMV]) mimic irAE symptoms and are understudied in this population. We aimed to describe the incidence, characteristics, treatment and outcomes of CMV infection in ICI-treated patients.MethodsWe conducted a single-center retrospective review of all adult patients who were CMV-positive after ICI therapy between 06/2011 and 05/2020. A CMV-positive non-ICI cohort was matched to the ICI group based on age, sex and cancer type. Variables of interest were collected through electronic medical records.ResultsThe study population comprised 192 patients overall. CMV infection incidence was 7.7% in ICI patients and 12.9% in non-ICI patients (P<0.001). Rates of infection clearance (83% vs. 50%, P=0.002) and recurrence (20% vs. 3%, P=0.037) were higher in ICI patients with hematologic vs. solid tumors, despite similar treatments. All-cause mortality was higher in solid rather than hematologic malignancies in ICI patients (83% vs. 54%, P=0.009); CMV-related mortality was low (3-4%) in both groups.ConclusionsCMV infection occurred in about 7.7% of the ICI-treated cancer population. The infection can be disseminated in multiple organs and has a wide spectrum of clinical symptoms. ICI-treated patients with a hematologic malignancy had higher viral clearance and recurrence than those with solid tumors. In this study, CMV itself did not lead to high mortality in cancer patients. Further study is needed to investigate the role of CMV infection in patients' irAEs and cancer outcome.
| S-EPMC9399572 | 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:BackgroundColorectal cancer (CRC) is a malignant tumor associated with a high mortality rate. While the advent of immune checkpoint inhibitors (ICIs) has been a gamechanger, only a small percentage of CRC patients benefit from ICIs. The pathological mechanism of CRC is not well understood, but somatic mutations, especially missense mutations, are believed to play an important role. This study examined the relationship between ICIs in colorectal cancer and missense mutations in the axonemal dynein heavy chain gene 7 (DNAH7).MethodsA clinical cohort (n=690) and the CRC data from the publicly available Cancer Genome Atlas (TCGA) were examined. Gene Set Enrichment Analysis, ESTIMATE analysis, and clinical correlation analysis were performed to explore the effects and mechanisms of DNAH7 mutation on immunotherapy in colorectal cancer.ResultsThe results showed that CRC patients with DNAH7 mutations can benefit more from ICIs (P<0.05). Patients with DNAH7 mutation had higher ESTIMATE scores, immune scores, and matrix scores, compared to patients without the DNAH7 mutation (P<0.001). The transport of small molecules, keratinization, asthma, autoimmune thyroid disease, allograft rejection, and other pathways were significantly enriched in DNAH7 mutated tissues (P<0.05). The top key genes associated with the DNAH7 mutation included AQP8, MS4A12, GUCA2B, and ZG16 (P<0.01).ConclusionsThe current study not only demonstrated the significance of DNAH7 as a risk factor and prognostic feature in CRC, but also revealed that DNAH7 mutations might affect the clinical efficacy of ICIs by impacting the tumor immune microenvironment.
| S-EPMC9843387 | biostudies-literature
Project description:ObjectiveThe 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 methodsThis 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.ResultsThe 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.ConclusionICIs 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.
| S-EPMC8100539 | biostudies-literature
Project description:Cancer patients are a vulnerable population in the current coronavirus disease 2019 (COVID-19) outbreak. The impact of immune checkpoint inhibitors (ICIs) on the outcomes of COVID-19 infection in cancer patients remains largely unclear. We retrospectively investigated all solid cancer patients who received at least one cycle of ICIs at a single institution between August 2020 and August 2021. All stage IV solid cancer patients who were on or ceased ICI treatment when diagnosed with COVID-19 were eligible. All COVID-19 infections were confirmed by RT-PCR. Risk factors for hospitalization, severe symptoms, and death were analyzed. A total of 56 patients were included in our study. Twenty (35.7%) patients require hospitalization, 12 (21.4%) developed severe symptoms, and 10 (17.9%) died from COVID-19 infection. ICI treatment was interrupted in 37 patients (66.1%), 24 of whom (64.9%) had treatment resumed. Eight (80%) COVID-19-related death occurred in unvaccinated individuals. Reinfection occurred in seven patients (12.5%), and three of them died from their second COVID-19 infection. Factors associated with hospitalization were high Charlson comorbidity score (OR 1.56, 95% CI 1.10-2.23, p = 0.01) and lymphocyte ≤ 1500 mm3 (OR 10.05, 95% CI 2.03-49.85, p = 0.005). Age, chemoimmunotherapy, and ICI treatment duration were not associated with increased risk of hospitalization, severe symptoms, or COVID-19-related mortality. ICI therapy does not impose an increased risk for severe COVID-19 infection in stage IV cancer patients. Vaccination should be encouraged among this population. Clinicians should be cognizant of a potential worse outcome in COVID-19-reinfected patients.
| S-EPMC9411835 | biostudies-literature
Project description:Immune checkpoint inhibitors (ICI) are revolutionizing care for cancer patients. The list of malignancies for which the Food and Drug Administration is granting approval is rapidly increasing. Furthermore, there is a concomitant increase in clinical trials incorporating ICI. However, the safety of ICI in patients undergoing surgery remains unclear. Herein, we assessed the safety of ICI in the perioperative setting at a single center. We conducted a retrospective review of patients who underwent planned surgery while receiving ICI in the perioperative setting from 2012 to 2016. We collected 30-day postoperative morbidity and mortality utilizing the Clavien-Dindo classification system. We identified 17 patients who received perioperative ICI in 22 operations. Patients were diagnosed with melanoma (n?=?14), renal cell carcinoma (n?=?2), and urothelial carcinoma (n?=?1). Therapies included pembrolizumab (n?=?10), ipilimumab (n?=?5), atezolizumab (n?=?5), and ipilimumab/nivolumab (n?=?2). Procedures included cutaneous/subcutaneous resection (n?=?6), lymph node resection (n?=?5), small bowel resection (n?=?5), abdominal wall resection (n?=?3), other abdominal surgery (n?=?3), orthopedic surgery (n?=?1), hepatic resection (n?=?1), and neurosurgery (n?=?2). There were no Grade III-IV Clavien-Dindo complications. There was one death secondary to ventricular fibrillation in the setting of coronary artery disease. ICI appear safe in the perioperative setting, involving multiple different types of surgery, and likely do not need to be stopped in the perioperative setting. Further studies are warranted to confirm these findings.
| S-EPMC5466999 | 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:Cancer vaccines have been exclusively studied all through the past decades, and have made exceptional achievements in cancer treatment. Few cancer vaccines have been approved by the US Food and Drug Administration (FDA), for instance, Provenge, which was approved for the treatment of prostate carcinoma in 2012. Moreover, more recently, T-VEC got approval for the treatment of melanoma. While, the overall therapeutic effects of cancer vaccines have been taken into consideration as below expectations, low antigenicity of targeting antigen and tumor heterogeneity are the two key limiting barriers encountered by the cancer vaccines. Nonetheless, recent developments in cancer immune-therapies together with associated technologies, for instance the unparalleled achievements bagged by immune checkpoint inhibitor based therapies and neo-antigen identification tools, envisage potential improvements in cancer vaccines in respect to the treatments of malignancies. This review brings forth measures for the purpose of refining therapeutic cancer vaccines by learning lessons from the success of PD-1 inhibitor based immune-therapies.
| S-EPMC5771333 | biostudies-literature