Immune Checkpoint Inhibitors In Cancer Patients Research Articles

Interplay of cachexia progression on the efficacy and toxicity of immune checkpoint inhibitors in patients with esophageal squamous cell cancer (ESCC): A longitudinal perspective.

e14629 Background: Immune checkpoint inhibitors (ICIs) have significantly improved the survival of patients with advanced esophageal squamous cell cancer (ESCC), however, the benefit of ICIs was limited to a few patients. It is vital to comprehend the factors influencing the response in order to identify patients who might benefit from ICIs. Cachexia, an intricate multifaceted syndrome characterized by the loss of skeletal muscle and substantial weight reduction, might impact on the immune response and efficacy of ICIs in cancer patients. The purpose of this study is to explore the impact of longitudinal dynamics of cachexia on the efficacy and adverse effect of ICIs for advanced ESCC patients. Methods: Advanced ESCC patients received at least two cycles of ICIs were enrolled from 2017 to 2021. The baseline and longitudinal changes of cachexia during ICI treatment were collected. Based on the longitudinal weight changes during ICI treatment, patients exhibiting cachexia at baseline were categorized into "reversible cachexia" and "irreversible cachexia" group, and patients without cachexia at baseline were also divided into "latent cachexia" and "cachexia-free" group. Kaplan-Meier curves and Cox regression analysis were performed to explore the impact of cachexia on the efficacy ICIs for ESCC patients. And chi-square test was used to evaluate the correlation between cachexia and immune-related adverse effects (irAEs). Results: A total of 278 individuals who had either received or were presently undergoing ICI treatment were enrolled, with the median progression free survival (PFS) of 5.8 months and overall survival (OS) of 8.3 months. Patients with cachexia before treatment had notably poorer outcomes, with median PFS of 7.9 vs 5.3 months (P=0.001), median time to progression (TTP) of 10.9 vs 6.1 months (P<0.001), and median OS of 14.3 vs 9.2 months (P=0.001). In terms of the longitudinal dynamics of cachexia, significantly inferior outcomes were observed for patients in irreversible cachexia compared to reversible cachexia, with the PFS of 4.4 months and 9 months (P<0.001), the TTP of 4.9 months and 9 months (P=0.006), and the OS of 7.8 months and 15 months, respectively (P=0.003). Although patients in latent cachexia group had inferior survival compared to cachexia-free group, no statistical difference was observed, with the PFS of 10.0 and 7.9 months and OS of 13.9 and 16.2 months. Besides, neither baseline nor longitudinal changes of cachexia was associated with irAEs for ESCC patients. Conclusions: This study indicated the impact of baseline and longitudinal cachexia on the efficacy of ICIs for advanced ESCC patients with ICIs. Dynamic monitoring and management of cachexia was recommended during the ICI treatment of ESCC patients.

Safety and efficacy of immune checkpoint inhibitors in patients with cancer and pre-existing autoimmune disease: A systematic review and meta-analysis in non-small cell lung cancer.

9053 Background: Cancer patients with pre-existing autoimmune diseases (AID) have been traditionally excluded from clinical trials of immune checkpoint inhibitors (ICI) due to concerns for immune activation leading to toxicity. As indications for ICI expand, there is a need for robust data on safety and efficacy of ICI in cancer patients with AID. Existing studies examined a heterogenous group of cancers and do not include a comparison to cancer patients without pre-existing AID. Therefore, data are lacking concerning how safety and efficacy of ICI in this group of patients may differ from the general population and whether the results are generalizable to non-small cell lung cancer (NSCLC). Methods: We searched for studies consisting of NSCLC, AID, ICI, treatment response, and adverse events using database-controlled vocabulary terms. We systematically searched Medline (PubMed), EMBASE, Scopus, CINAHL, and Web of Science. We selected studies that included NSCLC and excluded abstracts, case reports, review articles, and articles lacking outcomes or populations of interest. Three authors (WA, CL, NS) independently reviewed all abstracts to determine study eligibility and quality. Study quality was assessed using the Newcastle-Ottawa Scale. Study data were pooled using random-effects meta-analysis. Results: Data were extracted from 24 cohort studies, consisting of 10,924 cancer patients, of which 4353 were NSCLC patients. Studies examined a broad spectrum of AID consisting of 1157 patients, of which 291 were NSCLC patients. Pooled analysis revealed an AID flare incidence of 36% (95%CI 27%-46%) in all cancers and 23% (95%CI 9%-40%) in NSCLC. Tests of subgroup difference revealed no significant difference in AID flares by organ system in all cancers and NSCLC (p = 0.602 and p = 0.19, respectively). Pre-existing AID was associated with a higher risk of de novo iRAE in all cancer patients (RR 1.38, 95%CI 1.16-1.65) and in NSCLC patients (RR 1.51, 95%CI 1.12-2.03). There was no difference in de novo grade 3-4 iRAE and tumor response between cancer patients with and without AID. However, in NSCLC patients, pre-existing AID was associated with a 2-fold increased risk of de novo grade 3-4 iRAE (RR 1.95, 95%CI 1.01-3.75) but also better tumor response in achieving a complete or partial response (RR 1.56, 95%CI 1.19-2.04). Conclusions: Pre-existing AID confers an increased risk of toxicity during ICI therapy. NSCLC patients with AID are at a higher risk of de novo grade 3-4 iRAE but are also more likely to achieve treatment response than those without AID. Multidisciplinary collaboration is paramount when considering ICI therapy in this patient population with careful calculation of risk and benefit as well as close monitoring for toxicity.

Immune checkpoint inhibitors for the treatment of solid tumors in HIV-infected patients: is it worth the risk?

Objective. To present the available data regarding the tolerance of immune checkpoint inhibitors (ICIs) in cancer patients with concurrent HIV.Material and Methods. A literature search was conducted in the electronic databases PubMed, Cochrane Library and UpToDate up to February 2022.Results. The article outlines the background and experience of using ICIs for the treatment of malignant tumors in patients with concomitant HIV infection.Conclusions. Until recently, the presence of chronic infections, including HIV infection, was one of the key contraindications for prescribing immunotherapy. However, the recent scientific publications demonstrate the efficacy and good tolerability of ICIs in cancer patients with concurrent HIV. Future prospective clinical trials will help to predetermine the potential of immunotherapy in clinical practice in this patients.

Construction of a pyroptosis-related lncRNAs signature for predicting prognosis and immunotherapy response in glioma.

Recent studies have proved that pyroptosis-related long non-coding RNAs (PRlncRNAs) are closely linked to tumor progression, prognosis, and immunity. Here, we systematically evaluated the correlation of PRlncRNAs with glioma prognosis. This study included 3 glioma cohorts (The Cancer Genome Atlas, Chinese Glioma Genome Atlas, and Gravendeel). Through Pearson correlation analysis, PRlncRNAs were screened from these 3 cohorts. Univariate Cox regression analysis was then carried out to determine the prognostic PRlncRNAs. A pyroptosis-related lncRNAs signature (PRLS) was then built by least absolute shrinkage and selection operator and multivariate Cox analyses. We systematically evaluated the correlation of the PRLS with the prognosis, immune features, and tumor mutation burden in glioma. A total of 14 prognostic PRlncRNAs overlapped in all cohorts and were selected as candidate lncRNAs. Based on The Cancer Genome Atlas cohort, a PRLS containing 7 PRlncRNAs was built. In all cohorts, the PRLS was proved to be a good predictor of glioma prognosis, with a higher risk score related to a poorer prognosis. We observed obvious differences in the immune microenvironment, immune cell infiltration level, and immune checkpoint expression in low- and high-risk subgroups. Compared with low-risk cases, high-risk cases had lower Tumor Immune Dysfunction and Exclusion scores and greater tumor mutation burden, indicating that high-risk cases can be more sensitive to immunotherapy. A nomogram combining PRLS and clinical parameters was constructed, which showed more robust and accurate predictive power. In conclusion, the PRLS is a potentially useful indicator for predicting prognosis and response to immunotherapy in glioma. Our findings may provide a useful insight into clinically individualized treatment strategies for patients.

SECTM1 is upregulated in immuno-hot tumors and predicts immunotherapeutic efficacy in multiple cancers

Immune checkpoint inhibitors (ICIs) have transformed the management of advanced cancers. However, many patients could not benefit from ICIs therapy, and thus several biomarkers for therapeutic prediction have been uncovered. In this research, more than ten public and in-house cohorts were used to explore the predictive value and immunological correlations of secreted and transmembrane 1 (SECTM1) in cancers. SECTM1 expression was enhanced in tumors from patients with well immunotherapeutic responses in multiple cancers. In addition, SECTM1 was immuno-correlated in pan-cancer and enhanced in immuno-hot tumors. Invitro assays revealed that SECTM1 was upregulated by the IFN-γ/STAT1 signaling. Moreover, analysis of in-house immunotherapy cohorts suggested both tumor-expressed and circulating SECTM1 are promising biomarkers to predict therapeutic responses. Overall, this study reveals that SECTM1 is a biomarker of benefit to ICIs in cancer patients. Further studies including large-scale patients are needed to establish its utilization as a biomarker of benefit to ICIs.

CD8+ T cell-intrinsic IL-6 signaling promotes resistance to anti-PD-L1 immunotherapy

Although immune checkpoint inhibitors (ICIs) are established as effective cancer therapies, overcoming therapeutic resistance remains a critical challenge. Here we identify interleukin 6 (IL-6) as a correlate of poor response to atezolizumab (anti-PD-L1) in large clinical trials of advanced kidney, breast, and bladder cancers. In pre-clinical models, combined blockade of PD-L1 and the IL-6 receptor (IL6R) causes synergistic regression of large established tumors and substantially improves anti-tumor CD8+ cytotoxic T lymphocyte (CTL) responses compared with anti-PD-L1 alone. Circulating CTLs from cancer patients with high plasma IL-6 display a repressed functional profile based on single-cell RNA sequencing, and IL-6-STAT3 signaling inhibits classical cytotoxic differentiation of CTLs invitro. In tumor-bearing mice, CTL-specific IL6R deficiency is sufficient to improve anti-PD-L1 activity. Thus, based on both clinical and experimental evidence, agents targeting IL-6 signaling are plausible partners for combination with ICIs in cancer patients.

Comparative risk of acute kidney injury among cancer patients treated with immune checkpoint inhibitors

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.

Chronic hyperglycemia based on diabetes is independently associated with decreased survival in patients with advanced cancer treated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have started a new era in treating patients with cancer. The effect of comorbidities and concomitant drug use on ICIs have become of interest in those patients. Data about the impact of hyperglycemia on response to ICIs in cancer patients are limited. All advanced-stage cancer patients treated with ICIs in Ankara University Medical Oncology Department were retrospectively evaluated. Patients treated in expanded access programs or clinical trials were excluded from the study. A total of 137 patients were included in this study. The most common primary tumor type was malign melanoma (32.8%) and nivolumab (62.3%) was the most common used ICI. More than half of patients (57.7%) had lung metastasis at the initiation of ICIs. Thirty-five patients (25.5%) had diabetes before initiating ICIs. Median baseline fasting glucose level was higher in patients with diabetes than those without diabetes (117 mg/dl vs. 99 mg/dl, P = 0.002). In all patients, median overall survival and progression-free survival were 11.3 [95% confidence interval (CI), 8.1-14.4) and 5.9 (95% CI, 3.6-8.3) months, respectively. In multivariate analysis, diabetes was found to increase risk of death [hazard ratio (HR), 2.09; 95% CI, 1.27-3.43, P = 0.004) and disease progression (HR, 2.01, 95% CI, 1.29-3.09, P = 0.002). Hyperglycemia might decrease response to ICIs in patients with advanced cancer. This research area is still an unmet need in the immunotherapy era. Prospective studies are needed to elucidate the effect of hyperglycemia on the response to ICIs.

Safety of immune checkpoint inhibitors in patients with preexisting autoimmune disorders

In recent years, immune checkpoint inhibitors (ICIs) have been approved for a growing number of cancer types. Approximately a quarter of cancer patients have a concomitant diagnosis of autoimmune disorders (AID). Activation of the immune system with ICIs poses a potential risk of AID worsening, thus, the majority of the ICI clinical trials excluded these patients from the study. There is a paucity of data regarding the benefits and risks of ICIs in cancer patients with AIDs. The primary objectives of this study were to determine the incidence of immunotherapy-related AID worsening and all immunotherapy-related adverse events (irAEs). Secondary outcomes were time to AID worsening and survival difference. All adult patients (age >=18 years) with solid malignancy who received ICIs between Jan 2016 and June 2019 were identified using the University of Louisville pharmacy database. Medical records were reviewed to include all the patients with preexisting AIDs. Descriptive statistics were used to determine the incidence of AID worsening and all irAEs. Baseline characteristics were compared between cancer patients with vs without AID worsening using Pearson chi2 and Student's t-test, where appropriate. Multivariate Cox regression analysis was used to compare survival between the 2 groups. A total of 40 patients with AIDs were identified during the study period. The cancer types were melanoma (57.5%), lung (15%), breast (5%), and others (22.5%). AIDs were rheumatological (52.5%), dermatologic (20%), gastroenterological (12.5%), neurologic (12.5%), and hematological (2.5%). The incidence of all irAEs was 60% (grade >=3 in 20%) and AID worsening was 40% (grade >=3 in 15%). The median time from ICI initiation to AID worsening was 94.5 (range 21-431) days. In multivariate Cox regression analysis, adjusted for demographics, cancer type, and stage, survival was similar for patients who had AID worsening vs those who did not (HR 0.30 (95%CI 0.06-1.40, P = 0.128). In our single-institution study, cancer patients with preexisting AID do have an increased risk of irAEs with high-grade toxicities in 20% compared to historically reported 5% in the general cancer population. About 15% of patients reported grade >=3 worsening of their AIDs. Although the risk of irAEs is numerically higher in patients with AIDs, it may be acceptable to the patients if the potential benefits of ICIs outweigh the risks.

Impact of Immune Checkpoint Inhibitors on COVID-19 Severity in Patients with Cancer.

BackgroundAmid continued uncertainty about the management of cancer patients during the pandemic, this study sought to obtain real-world data on the use of immune checkpoint inhibitors (ICIs) before COVID-19 diagnosis and its association with severity and survival outcomes in cancer patients who contracted COVID-19.MethodsCancer patients diagnosed with COVID-19 were identified from a large electronic health record database; those treated with ICIs before COVID-19+ diagnosis were matched in a 1:2 ratio to those not treated with ICIs, using a 2-step matching procedure. A descriptive analysis examined the difference in COVID-19 mortality (30-day and overall) and severity outcomes between the 2 cohorts, and overall survival was compared.ResultsAmong 17 545 adults ≥18 years with cancer who tested positive for COVID-19 between February 20, 2020, and January 28, 2021, in the US, 228 ICI-treated patients were matched to 456 non-ICI-treated patients, comprising the 2 study cohorts. Clinical characteristics differed significantly between the 2 cohorts before matching, with metastatic disease, lung cancer, a history of smoking, and the presence of pulmonary comorbidities being more common in the ICI-treated cohort; after matching, the 2 cohorts were similar. There were no significant differences between the ICI-treated and non-ICI-treated cohorts for 30-day mortality (12.7% vs. 14.9%, P = .235), overall mortality (22.4% vs. 22.4%, P = 1.000), hospitalization (38.6% vs. 39.0%, P = .912), or emergency department visits (16.7% vs. 14.7%, P = .500). Overall survival was similar between the 2 cohorts.ConclusionThis analysis adds to the clinical evidence base that use of ICIs before SARS-CoV-2 infection does not affect COVID-19 severity or survival outcomes, supporting the continued use of ICIs in cancer patients during the pandemic.

Influence of Microbiome and Antibiotics on the Efficacy of Immune Checkpoint Inhibitors.

The human microbiome mainly consists of bacteria and interacts closely with the immune system. Immune checkpoint inhibitors (ICI) are used to treat several types of cancers. Recently, it has been identified that the gut microbiome plays a role in the effectiveness of immunotherapy. This study aims to analyze the effect of microbiome and antibiotics on the effectiveness of ICI in cancer patients and the measures to improve efficacy based on that. A detailed review was conducted on articles published in PubMed and Science Direct in the last five years i.e., 2016 to 2021. A total of 16 articles involving 1293 patients with cancer who were receiving immunotherapy, were deemed eligible to be included in the final review. Data were extracted from the eligible articles and were checked for quality appraisal. All 16 articles revealed the effect of either gut microbiome or antibiotics or both on ICI. Based on our findings, we found that the microbiome enriched in different microorganisms responded differently to the ICI and that antibiotics negatively impacted the effectiveness of ICI. The time at which patients receiving ICI were prescribed antibiotics influenced the effect of ICI. Antibiotics and different microbiome also affected progression-free survival (PFS) and overall survival (OS).

Safety of immune checkpoint inhibitors in patients with preexisting autoimmune disorders.

e14568 Background: In recent years, immune checkpoint inhibitors (ICIs) have been approved for a growing number of cancer types. Approximately 10-30% of cancer patients have a concomitant diagnosis of autoimmune disorders (AID). Activation of the immune system with ICIs poses a potential risk of AID worsening. The majority of the ICI clinical trials excluded these patients from the study. There is a paucity of data regarding the benefits and risks of ICIs in cancer patients with AIDs. The primary objectives of this study were to determine the incidence of immunotherapy related AID worsening and all immunotherapy related adverse events (irAEs). Secondary outcomes were time to AID worsening and survival difference. Methods: All adult patients (age ≥18 years) with solid malignancy who received ICIs between Jan 2016 to June 2019 were identified using the University of Louisville pharmacy database. Medical records were reviewed to include all the patients with preexisting AIDs. Descriptive statistics were used to determine the incidence of AID worsening and all irAEs. Baseline characteristics were compared between cancer patients with versus without AID worsening using Pearson chi2 and Student’s t-test, where appropriate. Multivariate Cox regression analysis was used to compared survival between the 2 groups. Results: A total of 40 patients with AIDs were identified during the study period. The cancer types were melanoma (57.5%), lung (15%), breast (5%), and others (22.5%). AIDs were rheumatological (52.5%), gastroenterological (12.5%), neurological (12.5%), dermatological (20%) and hematological (2.5%). The incidence of all irAEs was 60% (grade ≥3 in 20%) and AID worsening was 40% (grade ≥3 in 15%). Baseline characteristics of the 2 comparison groups are shown in table. The median time from ICI initiation to AID worsening was 94.5 (range 21-431) days. In multivariate Cox regression analysis, adjusted for demographics, cancer type, and stage, survival was similar for patients who had AID worsening versus those who did not (HR 0.30 (95%CI 0.06-1.40, p=0.128). Conclusions: In our single-institution study, cancer patients with preexisting AID do have an increased risk of irAEs with high-grade toxicities in 20% compared to historically reported 5% in the general cancer population; about 15% of patients reported grade ≥3 worsening of their AIDs. However, though the risk of irAEs is numerically higher in patients with AID, it may be acceptable to the patients if the potential benefits of ICIs outweigh the risks. Baseline demographics and clinical characteristics.[Table: see text]

Attitudes and Practices of Immune Checkpoint Inhibitors in Chinese Patients With Cancer: A National Cross-Sectional Survey.

Immune-checkpoint inhibitors (ICIs) are revolutionizing the field of immuno-oncology. Side effects and tumor microenvironment currently represent the most significant obstacles to using ICIs. In this study, we conducted an extensive cross-sectional survey to investigate the concept and practices regarding the use of ICIs in cancer patients in China. The results provide real-world data on the adverse events (AEs) of ICIs and the factors influencing the use of ICIs. This survey was developed by the Expert Committee on Immuno-Oncology of the Chinese Society of Clinical Oncology (CSCO-IO) and the Expert Committee on Patient Education of the Chinese Society of Clinical Oncology (CSCO-PE). The surveys were distributed using a web-based platform between November 29, 2019 and December 21, 2019. A total of 1,575 patients were included. High costs (43.9%), uncertainty about drug efficacy (41.2%), and no reimbursement from medical insurance (32.4%) were the factors that prevented the patients from using ICIs. The patients were most concerned about the onset time or effective duration of ICIs (40.3%), followed by the indications of ICIs and pre-use evaluation (33.4%). Moreover, 9.0, 57.1, 21.0, and 12.9% of the patients reported tumor disappearance, tumor volume reduction, no change in tumor volume, and increased tumor volume. Among the patients who received ICIs, 65.7% reported immune-related AEs (irAEs); 96.1% reported mild-to-moderate irAEs. Cancer patients in China had a preliminary understanding of ICIs. Yet, the number of patients treated with ICIs was small.

Sarcopenia and the risk of adverse events in patients treated with immune checkpoint inhibitors: a systematic review.

Sarcopenia has been associated with negative clinical outcomes in cancer patients, particularly response to treatment and survival. The exponential growth in the use of immune checkpoint inhibitors (ICIs) has led to an increase in the reporting of both adverse events in general (AEs) and immune-related adverse events (irAEs), which are unintended immune-related phenomenon that take place as a result of checkpoint blockade. However, there are no systematic reviews evaluating the relationship between sarcopenia and the risk of developing AEs and irAEs in cancer patients on ICI therapies. PubMed, MEDLINE, Embase, Cochrane and grey literature, repositories, websites Open Grey, Google Scholar, and abstracts of major international congresses were searched up to April 2020 for observational studies on sarcopenia and both AEs and irAEs in patients treated with ICIs. Study quality was assessed with The Newcastle-Ottawa quality assessment scale. PROSPERO registration number: CRD42020197178. One hundred and thirteen discrete articles were identified. Seven studies were included after evaluation of the eligibility criteria. Important sources of heterogeneity including the specific cut-points defining sarcopenia, sample size, inclusion and exclusion criteria, treatment regimen, and baseline demographics were evaluated and accounted for accordingly. Most of the included studies showed an increased risk of AEs with use of ICIs in cancer patients with sarcopenia, and in the majority of these, the increase was statistically significant. Due to the small number of available studies and the expanding use of ICIs, additional research is warranted.

Tumor-Associated Microbiome: Where Do We Stand?

The study of the human microbiome in oncology is a growing and rapidly evolving field. In the past few years, there has been an exponential increase in the number of studies investigating associations of microbiome and cancer, from oncogenesis and cancer progression to resistance or sensitivity to specific anticancer therapies. The gut microbiome is now known to play a significant role in antitumor immune responses and in predicting the efficacy of immune-checkpoint inhibitors in cancer patients. Beyond the gut, the tumor-associated microbiome—microbe communities located either in the tumor or within its body compartment—seems to interact with the local microenvironment and the tumor immune contexture, ultimately impacting cancer progression and treatment outcome. However, pre-clinical research focusing on causality and mechanistic pathways as well as proof-of-concept studies are still needed to fully understand the potential clinical utility of microbiome in cancer patients. Moreover, there is a need for the standardization of methodology and the implementation of quality control across microbiome studies to allow for a better interpretation and greater comparability of the results reported between them. This review summarizes the accumulating evidence in the field and discusses the current and upcoming challenges of microbiome studies.

1700P Perception and attitudes of Italian physicians towards the management of checkpoint inhibitors in oncology during COVID-19 outbreak: Results from a national survey

During the COVID-19 outbreak oncological care has been reorganized to face the emergency. Cancer patients have been reported to be at higher risk of severe events related to SARS-CoV-2. Moreover, there are concerns of a possible interference between immune checkpoint inhibitors (ICIs) and the pathogenesis of the infection. A 22-item questionnaire was shared with Italian physicians managing ICIs, between May 6 and 16, 2020. This survey aimed at exploring the perception about SARS-CoV-2 related risks in cancer patients receiving ICIs, and whether the management of these patients has been modified during COVID-19 outbreak. Respondents were 104, with a median age of 35.5 years, mainly females (58.7%), mainly working in Northern Italy (71%). 47.1% of respondents were afraid that a synergism could exist between ICIs mechanism of action and SARS-CoV-2 pathogenesis, leading to worse outcomes. 97.1% of respondents would not deny an ICI only for the possible occurrence of COVID-19. Measures for reducing hospital visits have been adopted by choosing the ICIs schedule with fewer administrations, adopting the highest labeled dose of each drug (55.8%) and/or choosing, among different ICIs for the same indication, the one with the longer interval between cycles (30.8%). 53.8% of respondents suggested the need to test for SARS-CoV-2 every cancer patient candidate to ICIs. Regarding differential diagnosis between immune-related adverse events (irAEs) and COVID-19 manifestations, 71.2% of respondents declared to manage a patient with onset of dyspnea and cough like a COVID-19 patient until otherwise proven (ie, waiting for the result of SARS-CoV-2 test before doing other diagnostic or therapeutic procedures); however, 96.2% did not reduce the use of steroids to manage irAEs during the pandemic. No major impact of COVID-19 on physicians’ attitudes towards the use of ICIs to manage specific clinical situations in different cancer types (ie, lung, breast, melanoma, urothelial) was observed. These results highlight the uncertainty of physicians dealing with ICIs in cancer patients during COVID-19 outbreak, supporting the need of dedicated studies on this regard.

Impact of corticosteroids use on efficacy of immune checkpoint inhibitors in cancer patients: A meta-analysis.

e15234 Background: Corticosteroids are commonly used for management of cancer-related symptoms or immune-related adverse events (irAEs) in cancer patients treated with immune checkpoint inhibitors (ICIs). However, given the inhibitory effects of corticosteroids on a broad range of immune responses, it is presumed that the use of these agents may affect the clinical outcomes of ICIs. This meta-analysis aims to explore the impact of corticosteroids use on the efficacy of ICIs in cancer patients. Methods: We conducted a search covering electronic databases (MEDLINE, EMBASE, and CENTRAL), conference abstracts (ASCO and ESMO) and reference lists to identify relevant studies. Studies that reported clinical outcomes of patients with corticosteroids administration before and/or after the initiation of ICIs treatment were eligible for evaluation. The primary outcomes included progression-free survival (PFS) and overall survival (OS). The random-effects model was utilized to synthesize the effect sizes of individual studies. Results: The initial literature search identified 1,900 records. After study selection, a total of 15 studies with 14,123 patients were included in the quantitative analysis. Corticosteroids use significantly reduced PFS (HR = 1.84; 95% CI: 1.30–2.61; P = 0.001) and OS (HR = 1.41; 95% CI: 1.18–1.68; P < 0.001) in cancer patients treated with ICIs. In subgroup analysis, corticosteroids use for cancer-related symptoms was associated with a shorter PFS (HR = 1.98; 95% CI: 1.40–2.78; P < 0.001) and OS (HR = 1.88; 95% CI: 1.25–2.83; P = 0.003), but their use for irAEs did not show a detrimental impact on OS (HR = 1.05; 95% CI: 0.77–1.44; P = 0.740). Conclusions: This meta-analysis indicated that corticosteroids use might hinder the efficacy of ICIs in cancer patients. The indications of corticosteroids use should be strictly controlled during the course of immunotherapy.

DNA damage and repair gene panel as a biomarker of immune checkpoint inhibitor response.

e15052 Background: Immune checkpoint inhibitors (ICIs) have become the standard of care in various cancers, although predictive biomarkers for efficacy still remain largely unknown. Methods: This study aims to develop a novel gene panel by selecting DNA damage and repair (DDR) genes from the Catalogue of Somatic Mutations in Cancer (COSMIC) database and perform validation using publicly available cohorts. Association between the DDR gene panel and tumor mutation burden or microsatellite status were analyzed from The Cancer Genome Atlas (TCGA) database. To further improve the clinical accessibility of the DDR gene panel, we analyzed the feasibility of its predictive value using cell free DNA in from 64 patients receiving ICIs. Results: The 193 mutated DDR genes in various cancers were chosen from the COSMIC databank, and the DDR genes found to individually predict a response rate > 50% in publicly melanoma cohort (Van Allen, et al) were selected. Eighteen DDR genes were selected as the DDR gene panel. The prevalence of the DDR gene mutations and predicted response rate of ICIs were validated in other three publicly available cohorts (Hugo et al, Synder et al, and Rizvi et al.). Tumor mutational burden and high microsatellite instability were positively associated with mutations of the 18 DDR genes for most cancers. Further validation was performed using cell-free DNA from cancer patients receiving ICIs. This DDR gene panel was detected in approximately 30% of various cancers, achieving a predicted response rate of approximately 60% in patients receiving ICIs. Conclusions: Our developed DDR gene panel can serve as a novel and reliable biomarker that can provide critical information for predicting the response to ICIs in cancer patients and guide the appropriate administration of ICIs in clinical practice.

Evaluation of the prognostic role of platelet-lymphocyte ratio in cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis

ObjectiveWhether platelet-lymphocyte ratio (PLR) is a prognostic factor for cancer patients treated with immunotherapy is under debate. In this study, we aimed to evaluate the relationship between PLR and survival of cancer patients treated with immune checkpoint inhibitors (ICIs). MethodsA systematical search was performed in databases including PubMed, Embase, and the Cochrane library to retrieve potential eligible clinical studies assessing the prognosis of cancer patients with high versus low PLR after immunotherapy, from the establishment of the database to June 2019. Quality evaluation of included studies was performed, and meta-analyses with regards to overall survival (OS) and progression-free survival (PFS) were conducted using RevMan 5.3 and STATA 11. ResultsA total of 12 eligible studies with 1340 cancer patients were included. Combined results showed that elevated PLR was a negative factor affecting the efficacy of ICIs in cancer patients. Patients with high PLR had a significantly shorter OS compared to those with low PLR (hazard ratio (HR) = 2.02, 95% confidence interval (CI): 1.46 to 2.80, P < 0.0001), as well as PFS (HR = 1.74, 95%CI: 1.27 to 2.38, P = 0.0006). Similar results were observed in sensitivity analyses. Subgroup analyses revealed that the prognostic role of PLR on OS and PFS was dependent on cancer type, region, and cutoff value. For NSCLC patients, the disease stage, ICIs agent, and line of treatment may not influence the prognostic role of PLR. ConclusionPLR could be a routinely potential prognostic factor for ICIs. Low PLR may be associated with better survival for cancer patients when treated with immunotherapy.

Safety of Immune Checkpoint Blockade in Patients with Cancer and Preexisting Autoimmune Diseases and/or Chronic Inflammatory Disorders

Abstract Background: Checkpoint blockade therapy, in the form of immune checkpoint inhibitors (ICIs), is increasingly being used to prolong survival in cancer patients, but its use is limited by the occurrence of immune-related adverse events (irAEs). These can be serious and occasionally fatal. However, the safety of ICIs is currently unknown in cancer patients with preexisting autoimmune diseases (PADs) and/or chronic inflammatory disorders (CIDs) such as eczema. Aim: The aim of this study is to evaluate the safety of ICIs in cancer patients with PAD and/or eczema at our institution. Patients and Methods: A retrospective study of cancer patients who presented to the Emergency Department between March 1, 2011, and February 29, 2016, after ICI therapy was previously conducted. Among these patients, those with PAD and/or eczema were further evaluated for safety by determining the occurrences of de novo irAEs or preexisting disease exacerbation. Results: Twenty-two cancer patients with PAD and/or eczema who received ICIs were reviewed, in which 15 were male (68%). Their median age was 63 years (range: 40–78 years). Most patients received anti-PD-1drugs (68%). Melanoma was the most common malignancy (45%). Autoimmune thyroiditis/primary hypothyroidism was the most common PAD. Four patients were receiving treatment for PAD at baseline using systemic corticosteroids, anti-inflammatory agents, and other immunosuppressants. Nineteen patients experienced de novo irAEs and/or PAD exacerbation. In three patients, the irAE was severe (grade ≥3). In six patients, the irAE or exacerbation was managed with systemic corticosteroids. Twelve patients experienced resolution of the de novo irAE or PAD exacerbation without the need to withhold or discontinue ICI therapy. The median time to last follow-up or death from the first dose of ICI was 16.8 months (range: 2–80 months). Death due to cancer progression was reported in 17 patients. Conclusion: Although de novo irAEs and PAD exacerbation were common, most patients with PAD and/or CIDs tolerated ICI therapy well.