Severity Of Immune-related Adverse Events Research Articles

COPD and Immune Checkpoint Inhibitors for Cancer: A Literature Review.

Immune checkpoint inhibitors are a standard treatment option for many patients with cancer and are most frequently used to treat lung cancer. Chronic obstructive pulmonary disease (COPD) is the most common comorbidity of patients with lung cancer. As the cancer-specific survival of patients with lung cancer continues to increase with modern treatments, it is critical to optimize comorbidities to improve overall survival. This literature review aimed to summarize current research on the impact of COPD upon immunotherapy outcomes. A comprehensive search was conducted in the PubMed database using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria focused on peer-reviewed articles published between 2010 and 2024 that addressed COPD, cancer, and immune checkpoint inhibitors. The study team screened the studies for relevance and then synthesized them narratively. This review identified 37 studies that met the inclusion criteria. Findings suggest that COPD is predictive of improved efficacy but slightly worse toxicity from immune checkpoint inhibitor therapy. The chronic inflammation of COPD leads to immune exhaustion including the overexpression of immune checkpoints on T-cells. Particularly within "hot" tumors that have higher concentrations of tumor-infiltrating lymphocytes, the COPD-related increase in programmed cell death protein 1 (PD-1) signaling likely creates sensitivity to immune checkpoint inhibitors. However, COPD can also lead to respiratory dysfunction, debility, and interstitial lung disease; each of which increases the severity of immune-related adverse events. COPD is a critical comorbidity that has a significant impact on many patients with cancer who receive treatment with immune checkpoint inhibitors. Future research is needed to design interventions to optimize COPD care in this high-risk patient population.

Lower respiratory tract microbiome is associated with checkpoint inhibitor pneumonitis in lung cancer patients.

The gut microbiome is associated with the occurrence and severity of immune-related adverse events (irAEs) in cancer patients undergoing immunotherapy. However, the relationship between the lower respiratory tract (LRT) microbiome and checkpoint inhibitor pneumonitis (CIP) in lung cancer patients who underwent immunotherapy is unclear. The aim of the present study was to investigate the associations between the LRT microbiome and CIP in lung cancer patients receiving immunotherapy. This retrospective study included lung cancer patients who received immunotherapy and had metagenomic next-generation sequencing (mNGS) results of LRT specimens [bronchoalveolar lavage fluid (BALF)]. Based on their final diagnosis, the patients were allocated to either the CIP group or the non-CIP group. We conducted an exploratory analysis of the LRT microbiome in the CIP and non-CIP patients, delineating the microbial composition, and comparing the differences between the two groups. In total, 52 lung patients were included in the study, of whom 33 were allocated to the CIP group and 19 to the non-CIP group. The alpha- and beta-diversity analyses revealed no significant differences between the two groups. In the CIP group, the dominant phyla were Firmicutes (41.7%), Acinetobacter (18.2%), and Proteobacteria (16.3%). In the non-CIP group, the dominant phyla were Firmicutes (38.2%), Acinetobacter (18.4%), and Proteobacteria (17.8%). Notably, the relative abundance of the Proteobacteria phylum (P<0.001) and Firmicutes phylum (P=0.01) was significantly higher in the CIP group than the non-CIP group. The elevated relative abundance of the Proteobacteria and Firmicutes phyla in the LRT samples is associated with CIP in lung cancer patients.

Immune-related adverse events in patients treated with immunotherapy according to corticosteroid exposure.

e14709 Background: Patients with cancer require treatment with corticosteroids for multiple reasons, including prevention of chemotherapy-related side effects. Although corticosteroid use has been associated with lower efficacy of immune checkpoint inhibitors (ICI) in some studies, whether corticosteroid exposure affects the presence and severity of immune-related adverse events (irAEs) remains unclear. Methods: Retrospective single-center study of patients diagnosed with solid tumors treated with ICI. Eligible patients were those who received at least one cycle of ICI and had at least 1 month of follow-up post-ICI initiation. Patient data were extracted from electronic medical records. Comparisons between groups were made based on steroid exposure (defined as the administration of &gt;10 mg of prednisone or its equivalent for &gt;10 days within a 30-day period or at any point during ICI treatment, excluding steroid treatment for irAEs). Associations between variables were assessed using independent samples T-test, Chi-square, and Fisher’s exact tests. Results: We included 135 patients (mean age 61 years, SD 13); 72 (54%) were male. Forty-two (31%) had been exposed to steroids (mean prednisone equivalent of 427 mg, SD 298). Most patients received ICI as palliative treatment for advanced disease (105/135; 78%), primarily as first-line therapy (79/105; 75%). Patients exposed to corticosteroids were more likely to have received ICI with chemotherapy (76% vs 1%, p&lt;0.001), were younger (56 vs. 63 years, p=0.009), more likely to be female (62% vs. 39, p=0.014), and had lower median Charlson Comorbidity Index scores (2 vs. 3, p=0.026). Steroid-exposed patients were more likely to have employed ICI in the neoadjuvant or adjuvant settings (36 vs. 16%, p=0.024) or as third or subsequent line therapy (26 vs. 8%, p=0.044). There were no statistically significant differences in the frequency of irAEs of any grade based on steroid exposure (31% vs 41%, p=0.252). However, patients who were exposed to steroids were significantly less likely to delay or suspend ICI (10% vs. 32%, p=0.005). No other parameters were associated with the rate or severity of irAEs. Conclusions: Our findings suggest that corticosteroid exposure does not increase the frequency of irAEs in patients treated with ICI, but it is associated with a reduced likelihood of discontinuing ICI due to irAEs. These observations suggest that corticosteroids may play a beneficial role in managing patients undergoing immunotherapy, particularly in sustaining treatment continuity despite irAEs. This study underscores the need for further investigation into optimal steroid use strategies to enhance patient outcomes with immunotherapy, especially in situations when they are commonly prescribed, such as premedication for chemotherapy.

44106 Effects of smoking status on incidence and severity of immune-related adverse events among patients with melanoma receiving immune checkpoint inhibitors

44106 Effects of smoking status on incidence and severity of immune-related adverse events among patients with melanoma receiving immune checkpoint inhibitors

43170 Comparative incidence and severity of immune-related adverse events among patients with melanoma on immune checkpoint inhibitors

43170 Comparative incidence and severity of immune-related adverse events among patients with melanoma on immune checkpoint inhibitors

Utilization and toxicity patterns of 2-weekly (Q2W) versus 4-weekly (Q4W) nivolumab for treatment of adjuvant and metastatic melanoma at BC cancer.

Nivolumab, an immune checkpoint inhibitor used to treat several malignancies, is associated with immune-related adverse events (IrAEs). Original dosing for melanoma was 3 mg/kg (maximum 240 mg) every 2 weeks (Q2W). Based on simulation studies depicting similar efficacy and toxicity to original dosing, extended interval dosing of 6 mg/kg (maximum 480 mg) every 4 weeks (Q4W) was introduced. This study will compare safety between Q2W and Q4W dosing at BC Cancer in melanoma patients. Retrospective chart review for reported incidence, onset, and severity of IrAEs in melanoma patients treated with nivolumab Q2W and Q4W dosing was completed. Fisher's test was conducted for first incidence IrAEs using Microsoft Excel. Seventy-one patients were identified (Q2W n = 35, Q4W n = 36). Baseline characteristics were similar in both groups. No statistically significant difference was found in incidence of IrAEs between Q2W and Q4W dosing (Q2W 40% vs Q4W 50%, p = 0.477). Rash was most common (Q2W 79% vs Q4W 50%) followed by hypothyroidism (Q2W 33% vs Q4W 20%). Median onset of IrAEs seemed later with Q4W dosing (Q2W cycle 1 vs Q4W cycle 4). Regardless of dosing, most IrAEs were grade 1-2 in severity (Q2W 100% vs Q4W 89%). Q4W dosing is associated with comparable incidence and potentially later onset of IrAEs compared to Q2W dosing. Most IrAEs in both dosing groups were similar and mild. Therefore, Q4W dosing offers a safe alternative to Q2W dosing while providing benefits including decreased workload for staff, decreased clinic visits, and viral exposure by patients.

Comparative analysis of immune-related adverse events among patients with melanoma on immune checkpoint inhibitors: A retrospective cohort study.

In a large, multi-institutional cohort of 672 patients with melanoma, we examined the comparative incidence and severity of immune-related adverse events among patients receiving first-line immune checkpoint inhibitors. Comparing PD-1 inhibitors, nivolumab was associated with significantly lower risk of high-grade toxicity onset compared with pembrolizumab on unadjusted logistic regression analysis. Compared with pembrolizumab, use of the CTLA-4 inhibitor ipilimumab was associated with a significant increase in risk of gastrointestinal, but not endocrine and cutaneous toxicities.

An assessment of extended pembrolizumab dosing in advanced non-small-cell lung cancer in the COVID-19 pandemic.

Background: There are limited clinical data comparing extended dosing (ED) versus standard dosing (SD) of pembrolizumab for metastatic non-small-cell lung cancer. Methods: This retrospective study included patients with metastatic non-small-cell lung cancer and PD-L1 tumor proportion score ≥50% treated with one or more cycles of single-agent pembrolizumab with SD or ED from January 2018 to December 2020. Results: A higher proportion of patients were alive in the ED group (vs SD) at 6months (94 vs 51%), 12months (94 vs 33%) and data cutoff (94 vs 26%) (p<0.001 for all). The rate (44 vs 32%; p=0.407) and severity of grade ≥3 immune-related adverse events were similar (50 vs 52%); however, ED patients more frequently discontinued treatment due to toxicity (45 vs 15%; p<0.001). Conclusion: A greater proportion of ED patients were alive at data cutoff, and the rate and severity of immune-related adverse events were similar between groups.

Association Between the Severity of Immune-related Adverse Events and the Prognosis in Patients With Non-small Cell Lung Cancer Receiving Treatment With Immune Checkpoint Inhibitors.

Among patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI), survival is reported to be longer in those experiencing immune-related adverse events (irAEs). We evaluated the progression-free survival (PFS) in the absence of further treatment after ICI therapy was discontinued because of the emergence of irAEs in patients with NSCLC. Data from patients with NSCLC in whom ICI therapy was discontinued because of the development of irAEs were retrospectively analyzed. The primary endpoint was the PFS from the last day of administration of ICIs, in the absence of any further treatment. A total of 162 patients with NSCLC received treatment with ICIs between January 2016 and December 2021. Among them, ICI therapy was discontinued in 33 patients because of the appearance of irAEs. The median (95% confidence interval) PFS in the absence of any treatment after the last administration of ICIs was 7.2 (4.2-12.3) months. According to the Common Terminology Criteria for Adverse Events, the Cox proportional hazards model was used to identify the severity of irAEs, which were determined to be significantly associated with the PFS in the absence of any further treatment after the last administration of ICI therapy. Although the present study showed that the PFS in patients with NSCLC was relatively long in the absence of any further treatment after the last administration of ICIs, the PFS was associated with the severity of the irAEs, and some patients showed early disease progression or death.

The study of immune-related adverse events in a community-based centre.

2642 Background: The effectiveness of immunotherapy is often hindered by the development of immune-related adverse events (IrAE). Racial minorities were under-represented in the key clinical trials that led to the approval of different immune checkpoint inhibitors (ICI). In this study, we explore the side effect profile of immune checkpoint inhibitors in our patient population that comprises almost entirely of minorities, mostly African Americans (AA) and Hispanics. We hypothesize that due to race-based differences in immune milieu of the body and disease susceptibility, the timing and severity of immunotherapy-related IrAE would be different in AA and Hispanics compared to Caucasians. This can translate into a difference in clinical outcomes as well. There have been some suggestions of a positive association of the development of IrAE with cancer survival, although the data is limited and heterogeneous. The purpose of our study is to study the frequency and severity of IrAEs in racial minority groups, compare them with previous clinical trials population, and add valuable real-world data in this underrepresented group of patients. Methods: A retrospective chart review was performed on adult patients with solid malignancies treated with any ICI between January 1, 2015 and April 30, 2022. Patients were classified according to age (greater/equal to 65y or younger), sex, race (self-identified), primary cancer, and type of immunotherapy received. Outcome data using type and severity of IrAE, time to development of IrAE, and any association with clinical outcomes was collected and analyzed using descriptive statistics as well as univariate analysis. Results: A total of 78 patients were included in the final analysis. The mean age was 68 years; 51% were males; 42.3% were Hispanics, 37% were AA, 19.7% were others, and 1% were Whites. Most common malignancy was lung cancer (65.5%). Most common ICI agent used was Pembrolizumab (n = 52) and 2 patients were treated with combination therapy using Ipilimumab and Nivolumab. 41 (52.5%) patients had IrAE of any grade while 9 (11.5%) patients experienced grade 3 side effects. None of the patients experienced grade 4 side effects. Most common IrAE of any grade was hypothyroidism (n = 14) while most common grade 3 side effect was colitis (n = 6). 31 patients were less than 65y of age. There was no significant difference in IrAE in patients less than 65 years of age vs ≥ 65 years (51.6% vs 53.1%) or grade 3 IrAE (9.6% vs 12.7%). Conclusions: In our study population consisting mostly of AA and Hispanics, the rate of IrAE of any grade as well as grade 3 or 4 IrAE with ICI therapy was comparable to what was seen in clinical trials involving these drugs. This data and its potential effects on survival outcomes need to be analyzed in prospective studies involving a larger number of patients.

Gut microbiota composition in patients with advanced malignancies experiencing immune-related adverse events.

The gut microbiota is implicated in the occurrence and severity of immune-related adverse events (irAEs), but the role it plays as well as its causal relationship with irAEs has yet to be established. From May 2020 to August 2021, 93 fecal samples were prospectively collected from 37 patients with advanced thoracic cancers treated with anti-PD-1 therapy, and 61 samples were collected from 33 patients with various cancers developing different irAEs. 16S rDNA amplicon sequencing was performed. Antibiotic-treated mice underwent fecal microbiota transplantation (FMT) with samples from patients with and without colitic irAEs. Microbiota composition was significantly different in patients with and without irAEs (P=0.001) and with and without colitic-type irAEs (P=0.003). Bifidobacterium, Faecalibacterium, and Agathobacter were less abundant and Erysipelatoclostridium more abundant in irAE patients, while Bacteroides and Bifidobacterium were less abundant and Enterococcus more abundant in colitis-type irAE patients. Major butyrate-producing bacteria were also less abundant in patients with irAEs than those without (P=0.007) and in colitic vs. non-colitic irAE patients (P=0.018). An irAE prediction model had an AUC of 86.4% in training and 91.7% in testing. Immune-related colitis was more common in colitic-irAE-FMT (3/9) than non-irAE-FMT mice (0/9). The gut microbiota is important in dictating irAE occurrence and type, especially for immune-related colitis, possibly by modulating metabolic pathways.

Prognostic Significance of the Severity of Immune-Related Adverse Events in Advanced Cancer Patients Treated with PD-1/PD-L1 Inhibitors: A Real-World Data Analysis.

There is limited evidence regarding immune-related adverse events (irAEs) in Asian cancer patients treated with antibodies directed against programmed cell death-1 (PD-1) or programmed cell death-ligand 1 (PD-L1). This study aimed to investigate the clinical patterns and prognostic significance of grade 1-2 and grade ≥ 3 irAEs by PD-1/PD-L1 inhibitors in cancer patients using real-world clinical data. We conducted a retrospective study of cancer patients who received pembrolizumab, nivolumab, or atezolizumab at a tertiary hospital in South Korea. Incidence, time to onset, and grade 1-2 and grade ≥ 3 irAE risk factors were analyzed from medical records. The association of irAE severity with progression-free survival (PFS) and prognostic factors for PFS were evaluated. Among a total of 431 patients, irAEs occurred in 45.2%, and 9.5% were grade ≥ 3 irAEs. There were no significant differences in the median time to onset based on severity. Risk factors for the development of grade ≥ 3 irAEs were the presence of autoimmune disorders or diabetes mellitus. The median PFS was significantly different at 13.20, 9.00 and 4.17 months for the grade 1-2, grade ≥ 3, and no irAE groups, respectively. An increase in administration cycles was associated with a reduced risk of progression in patients with grade 1-2 and grade ≥ 3 irAEs. The development of grade ≥ 3 irAEs was affected by comorbidities and associated with improved PFS compared with those without irAEs. Our findings identified the real-world epidemiology, risk factors, and prognostic significance of irAEs, which may guide treatment decisions of PD-1/PD-L1 inhibitors.

Associations of influenza vaccination with severity of immune-related adverse events in patients with advanced thoracic cancers on immune checkpoint inhibitors.

BackgroundWhether influenza vaccination (FV) is associated with the severity of immune-related adverse events (IRAEs) in patients with advanced thoracic cancer on immune checkpoint inhibitors (ICIs) is not fully understood.MethodsPatients enrolled in this retrospective cohort study were identified from the Vanderbilt BioVU database and their medical records were reviewed. Patients with advanced thoracic cancer who received FV within 3 months prior to or during their ICI treatment period were enrolled in the FV-positive cohort and those who did not were enrolled in the FV-negative cohort. The primary objective was to detect whether FV is associated with decreased IRAE severity. The secondary objectives were to evaluate whether FV is associated with a decreased risk for grade 3–5 IRAEs and better survival times. Multivariable ordinal logistic regression was used for the primary analysis.ResultsA total of 142 and 105 patients were enrolled in the FV-positive and FV-negative cohorts, respectively. There was no statistically significant difference in patient demographics or cumulative incidences of IRAEs between the two cohorts. In the primary analysis, FV was inversely associated with the severity of IRAEs (OR 0.63; p=0.046). In the secondary analysis, FV was associated with a decreased risk for grade 3–5 IRAEs (OR 0.42; p=0.005). Multivariable Cox regression showed that FV was not associated with survival times.ConclusionsOur study showed that FV does not increase toxicity for patients with advanced thoracic cancer on ICIs and is associated with a decreased risk for grade 3–5 IRAEs. No statistically significant survival differences were found between patients with and without FV.

Safety and efficacy of immune checkpoint inhibitors in non-small cell lung cancer patients with preexisting antinuclear antibodies: a retrospective cohort study.

BackgroundAntinuclear antibodies (ANAs) predicting the safety and efficacy of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) are still a matter of debate considering previous studies showed quite different results based on different ANA cut-off values. Thus, we investigated the associations between different ANA titers and the safety and efficacy of ICIs. Moreover, we also briefly discussed the effects of anti-thyroglobulin (ATG) and anti-thyroid peroxidase (ATPO) on the safety of ICIs.MethodsA total of 159 Chinese patients confirmed to have locally-advanced or metastatic NSCLC given ICIs or chemoimmunotherapy in Peking Union Medical College Hospital from January 2015 to December 2020 were analyzed retrospectively and were followed up until December 2020 or death or loss to follow-up. Patients’ characteristics were retrieved from medical records. ANAs were detected by the indirect immunofluorescence assay, ATG and ATPO by the electrochemiluminescence immunoassay. The severity of immune-related adverse events (irAEs) was graded according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0) and the efficacy was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).ResultsThe incidence of irAEs, median progression-free survival (mPFS) of the ANA negative and positive groups were 26.0% vs. 31.4% (P=0.457), 17.7 vs. 10 months (P=0.603) for the cut-off value of 1:80; 26.2% vs. 33.9% (P=0.305), 11.9 vs. 10.6 months (P=0.957) for 1:160; and 25.9% vs. 45.8% (P=0.047), and 11.9 vs. 7.7 months (P=0.471) for 1:320, separately. Besides, ANA titer ≥1:320 was associated with irAEs [odds ratio (OR) =4.9, 95% confidence interval (CI): 1.45–16.52, P=0.01] and the incidence of adverse skin reactions differed greatly between the negative and positive groups (9.7% vs. 32%, P=0.003). Moreover, a total of 52 out of 159 patients were tested for ATG and ATPO. 46 patients were negative and 6 were positive, with the incidence of abnormal thyroid function being 4.3% vs. 50% (P=0.005), respectively.ConclusionsPreexisting ANAs may not correlate with the clinical benefit of immunotherapy in patients with NSCLC but may be associated with adverse skin reactions. Besides, ATG or ATPO has the potential to predict thyroid dysfunction.

Abstract 662: Late CTLA-4 Ig treatment improves antitumor efficacy of immunotherapy

Abstract The promising approach of combining immune checkpoint therapies such as anti-CTLA-4 and anti-PD-1 increases antitumor response and overall survival rate relative to single treatments. However, it also increases the frequency and severity of immune-related adverse events (irAEs), such as cardiotoxicity. Our previous results showed that CTLA-4 Ig (abatacept), an inhibitor of T cell costimulation through CD28, can reverse those irAEs in patients with cancer, however, its effect on the antitumor response remains unclear. In the B16F10 melanoma model, we injected mice with CTLA-4 Ig antibody when: 1) mice were first treated with anti-CTLA-4, anti-PD-1, or combination (early time point) and 2) the immunotherapy was finished (late time point). We demonstrated that CTLA-4 Ig at the early time point compromised the antitumor efficacy of the immunotherapy. In contrast, the antitumor efficacy of the immunotherapy was improved if mice were treated with CTLA-4 Ig at the late time point. We also found that the antitumor response induced by CTLA-4 Ig (late) was dependent on CD80/86. Interestingly, the frequency of ICOS+ Foxp3+ Tregs was significantly reduced by CTLA-4 Ig at the late time point. Thus, we treated B16F10 tumors in Foxp3DTR mice with anti-CTLA-4 and then with CTLA-4 Ig (late). The antitumor tumor efficacy was similar between mice treated with or without Diphtheria toxin (DT) at the late time point. This suggests that the improved antitumor efficacy of CTLA-4 Ig at the late time point was Treg dependent. Collectively, we show that CTLA-4 Ig treatment has a differential role throughout the time course of immunotherapy treatments, and this work suggests a potential combination treatment strategy with checkpoint blockade and late CTLA-4 Ig treatment. Citation Format: Stephen Mok, James P. Allison. Late CTLA-4 Ig treatment improves antitumor efficacy of immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 662.

PD-1 Blockade After Avelumab in Relapsed/Refractory Classical Hodgkin Lymphoma

BackgroundAnti-PD-1 directed therapy is safe and effective in patients with relapsed/refractory (r/r) cHL and is currently being studied in the frontline setting. There are currently little data regarding the safety and efficacy of PD-1 blockade after prior PD-L1 blockade with agents such as avelumab. MethodsThis is a retrospective case series evaluating r/r cHL patients treated with avelumab who subsequently received at least 1 dose of PD-1 blockade. Primary objective is efficacy as measured by overall response rate. Secondary objectives include duration of response and time to progression on PD-1 blockade as well as safety as evaluated by incidence and severity of immune-related adverse events (irAE) with PD-1 blockade. ResultsThere were 7 patients treated with PD-1 blockade after avelumab, of whom 4 were re-treated. The median follow-up was 46.8 months. At the time of PD-1 blockade initiation median age was 36.6 years, all patients had advanced stage, 1 patient had B symptoms, and 4 patients had extranodal disease. Patients received median 7 prior lines of therapy including avelumab. Median duration on anti-PD-1 treatment was 15.9 months. A response was observed in 86% of patients with median duration of response of 26.4 months and median time to progression of 22.2 months. Only 1 patient experienced an irAE (grade 2 pneumonitis). ConclusionOur study suggests that PD-1 blockade after PD-L1 blockade in r/r cHL appears safe and may be effective with durable responses observed in a subset of patients.

Effect of influenza vaccination on immune-related adverse events in patients receiving single-agent immune checkpoint inhibitors for the treatment of cancer.

e18763 Background: Recent single-center, retrospective reviews have evaluated the effect of influenza vaccinations on the incidence and severity of immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors (ICI). Methods and outcomes in these studies vary. The most common medication investigated was ipilimumab, an Anti-CTLA-4 monoclonal antibody. There is limited data evaluating the incidence of irAEs in those receiving the specific ICIs, program death-1 (PD-1) and program death ligand-1 (PD-L1) inhibitors. Methods: A retrospective chart review was conducted including patients 18 to 89 years old who received single-agent pembrolizumab, nivolumab, atezolizumab, or durvalumab at an academic medical center from August 2015 to August 2019. The primary objective was to evaluate the incidence of irAEs in those who received an influenza vaccine compared to those who did not. Electronic health records, and the Louisiana Immunization Network for Kids (LINKS), which now collects adult information, were utilized for data collection. Chi-square tests were used to evaluate all endpoints. Results: Of the 217 charts screened, 133 were included in this study Fifty-three patients were included in the influenza vaccination group and 80 patients in the group that did not receive influenza vaccinations. The median age in those who received an influenza vaccine and in those who did not were 61 years and 62 years, respectively. The most common cancer diagnoses were lung cancer and melanoma. Ninety-one percent of patients in the vaccination group versus 81% in the group who did not receive an influenza vaccine received either nivolumab or pembrolizumab (PD-1 inhibitors). There was no statistical difference in irAEs in those who received an influenza vaccine versus those who did not (30% versus 45%, p = 0.15). The only significant secondary outcome found was the rate of irAEs in patients receiving a PD-1 inhibitor versus a PD-L1 inhibitor regardless of vaccination (42.2% versus 11.1%, p = 0.03). The majority of irAEs were grade 1 or 2. Conclusions: Based on this study, receiving an influenza vaccine does not have an influence on the risk of irAEs in those receiving ICI, specifically PD-1 and PD-L1 inhibitors. These outcomes may have been affected by adherence issues with yearly influenza vaccinations, inaccurate vaccine records, and receiving vaccines out of state. The statistically significant secondary outcome may have been affected by the disproportionate number of patients who were receiving a PD-1 inhibitor in this study. Larger population studies are needed to validate these findings and identify both the risk and benefit of patients receiving their yearly influenza vaccine while receiving ICI.

Immune-related toxicities in NSCLC: Real-world experience from a tertiary cancer center

Abstract Background Immune checkpoint inhibitors (ICIs) are key in the treatment of advanced non-small cell lung cancer (NSCLC). However, there is a paucity of large real-world case series on timing and severity of immune-related adverse events (irAEs) that could inform treatment service provision. Methods A retrospective study of patients with advanced NSCLC treated with ICIs at The Clatterbridge Cancer Centre between 2016 and 2018 was conducted to review irAEs in the context of therapeutic efficacy. Kaplan Meier analysis, Mann-Whitney and chi-squared tests were used. Results 303 patients were identified. Median age was 68 years; 83 patients (27%) had a performance status (PS) of 0; 85 (28%) had an ACE-27 comorbidity score ≥2. 277 (91%) had pembrolizumab (107 (35%) first line), 21 (7%) nivolumab and 5 (2%) atezolizumab. Median number of cycles was 6 (range 1-29). Median progression-free and overall survival (PFS/OS) were 5.0 and 10.0 months. IrAEs were reported in 40% of patients and 13% experienced multiple irAEs; 11% were ≥G3. The most common irAEs were dermatitis (12%), dysthyroidism (9%), colitis (6%), hepatitis (5%), arthralgia (5%), pneumonitis (5%); the most common ≥G3 irAEs were pneumonitis (3%), hepatitis (2%) and colitis (2%). Treatment was discontinued due to irAEs in 12% of patients. Median time to irAEs onset by system involved varied between 46 days (hyperthyroidism) and 122 days (arthralgia). There was no association between irAEs and age (p = 0.16), PS (p = 0.46), or ACE-27 score (p = 0.68). 83% of irAEs occurred within 6 months of initiating ICIs; no clear correlation between irAEs incidence and time on treatment was found. Patients with irAEs within 6 months of treatment had longer PFS (7.1 vs. 3.9 months, HR 0.70, p = 0.014) and OS (15.6 vs. 7.7 months, HR 0.48, p Conclusion In our large real-world retrospective cohort study the incidence of irAEs reflected that seen in clinical trials. There appears to be a toxicity-efficacy relationship with irAEs; however, larger studies are required to validate this. Legal entity responsible for the study The Clatterbridge Cancer Centre NHS Foundation Trust. Funding Has not received any funding. Disclosure A.C. Olsson-Brown: Honoraria (self): MSD; Honoraria (self), Research grant / Funding (self): Roche; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Research grant / Funding (self): Eli Lily; Research grant / Funding (self): Novartis. C. Escriu: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): AstraZeneca; Advisory / Consultancy: MSD; Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (self): Boeringher Ingelheim; Speaker Bureau / Expert testimony: Pfizer. All other authors have declared no conflicts of interest.

1806 When the Cure Is the Cause: Checkpoint Inhibitor-Induced Lymphocytic Esophagitis

INTRODUCTION: Immune checkpoint inhibitors are a group of novel treatment agents that are used for the treatment of multiple metastatic malignancies. Among these are programmed cell death 1 receptor (PD-1) antibodies that promote T cell proliferation, activating the immune response to tumor cells as well as non-tumor cells causing immune-related adverse events (irAEs). Diarrhea and colitis are common irAEs. Upper gastrointestinal involvement is rare with esophagitis limited to only case reports. CASE DESCRIPTION/METHODS: A 74-year-old female with metastatic renal cell carcinoma developed throat pain and dysphagia after 10 doses of Nivolumab. Proton pump inhibitor (PPI) and viscous lidocaine improved her symptoms. After 20 doses of therapy she developed odynophagia and dysphagia to both liquids and solids. She underwent an esophagogastroduodenoscopy which revealed esophagitis of 13 cm in length, manifest as circumferential erythema and exudate. Biopsy confirmed active esophagitis with dyskeratotic keratinocytes and lymphoplasmacytic infiltrate. Immunohistochemistry demonstrated markedly increased polyclonal plasma cells. This was consistent with nivolumab-induced esophagitis. Nivolumab was discontinued and she was started on methylprednisolone, with rapid improvement in symptoms and subsequent transition to prednisone. She was treated with a prolonged 3-month taper, but her dysphagia to solids recurred 2 months after completing the steroids. Repeat endoscopic biopsies were consistent with reflux esophagitis. She was treated with topical steroids for suspected residual Nivolumab-induced esophagitis as well as PPI with improvement in symptoms. Ten months later, the patient developed dyspepsia and early satiety. Repeat endoscopy showed discolored, linearly eroded, friable, sloughing mucosa. Biopsies taken revealed active and chronic esophagitis with lymphocytic infiltrate again consistent with Nivolumab-induced esophagitis. The patient symptomatically improved with sucralfate and PPI, and treatment was not further escalated. DISCUSSION: This is a rare case of Nivolumab-induced esophagitis demonstrating initial improvement with prolonged steroid taper followed by recurrent symptoms and persistent endoscopic disease treated with acid suppression, sucralfate and topical steroids. For refractory symptoms of esophagitis, immunosuppressants such as Infliximab could be considered. It is important to recognize the diversity and severity of immune-related adverse events to avoid incomplete treatment or a delay in therapy.

Immune checkpoint inhibitor toxicity in the clinical practice setting.

e14128 Background: Immune checkpoint inhibitors (ICIs) are changing the landscape of treatment in oncology. The use of ICIs is growing rapidly as the indications for these medications broaden and new ICIs become approved. Given the rapid growth and relative infancy of the use of ICIs, much information stands to be gained on their use in the clinical practice setting, especially regarding toxicity. Methods: The primary objective of this project was to examine the incidence and severity of immune-related adverse events (irAEs), after treatment with single-agent or combination ICIs at a multi-site community cancer center. A retrospective chart review was conducted on all patients who had received ipilimumab, nivolumab, pembrolizumab, atezolizumab, or ipilimumab plus nivolumab from May 1, 2011 to June 30, 2017. Data collected included patient demographics, disease state, treatment information, preexisting autoimmune disease, previous immunotherapy, and adverse event details. The results were analyzed using descriptive statistics. Results: Data was collected on 383 patients. Dermatologic irAEs were common across single agent ICIs (overall incidence 23%). Diarrhea and/or colitis incidence was highest with CTLA-4 inhibitor ipilimumab (26% at 3 mg/kg and 22% at 10 mg/kg) versus the other monotherapy PD-1/PDL-1 inhibitors. Endocrinopathies were most common with ipilimumab 10 mg/kg (55%) and pneumonitis incidence was highest with nivolumab (6%). ICI toxicity occurred in 63% of patients with preexisting autoimmune disease versus 54% of those without a baseline autoimmune disease. Incidence of hospitalization and treatment holds due to irAEs was higher with combination therapy (57% and 66%, respectively) than with monotherapy (10% and 24%, respectively). Conclusions: Overall, there was increased incidence in ICI toxicity in patients at this oncology institution versus what has been reported in clinical trials. Patients with preexisting autoimmune diseases appeared to have mainly low-grade toxicities with slightly increased incidence of irAE compared with those without pre-existing autoimmune disease. Treatment holds and hospitalizations were higher in patients treated with combination therapy ICIs compared to monotherapy ICIs.