Uncovering the Burden of Immune-Related Adverse Events in Immunotherapy: Insights from a Nationally Representative Sample.

BACKGROUND: Immune checkpoint inhibitors have shown promising efficacy in multiple malignancies and, therefore, have been increasingly used over the past decade. Clinical data have suggested anti-cancer efficacy associated with immune-related adverse events that could have added healthcare resource utilization and costs. OBJECTIVE: We used a nationwide dataset to investigate the association between immune-related adverse events and healthcare resource utilization, charges, and mortality among patients receiving various immune checkpoint inhibitors for indicated cancers. METHODS: We performed a retrospective analysis of the National Inpatient Sample to identify patients hospitalized in the USA for immunotherapy between October 2015 and 2018. Data between patients who developed immune-related adverse events were compared to those who did not. Baseline characteristics, inpatient complications, and associated charges were collected and analyzed between these two groups. RESULTS: Patients who developed immune-related adverse events in the hospital had high incidences of acute kidney injury, non-septic shock, and pneumonia, and managing these complications significantly contributed to higher healthcare resource utilization. The average charge of admission was highest in patients who developed an infusion reaction, followed by colitis, and adrenal insufficiency. In terms of cancer type, renal cell carcinoma had the highest charges, followed by Merkel cell carcinoma. CONCLUSIONS: Immune checkpoint inhibitor-based regimens have shifted the treatment landscape among multiple malignancies and their use continues to expand. However, a significant proportion of patients still develop severe adverse effects leading to increased healthcare costs and impacting patients' quality of life. Closer attention should be given to recognizing and managing immune-related adverse events according to guidelines across healthcare facilities and clinical practice settings.

Association of Immune Checkpoint Inhibitors With Neurologic Adverse Events: A Systematic Review and Meta-analysis.

Importance: Neurologic adverse events (NAEs) due to immune checkpoint inhibitors (ICIs) can be fatal but are underexplored. Objective: To compare NAEs reported in randomized clinical trials (RCTs) of US Food and Drug Administration-approved ICIs with other forms of chemotherapy and placebo. Data Sources: Bibliographic databases (Embase, Ovid, MEDLINE, and Scopus data) and trial registries (ClinicalTrials.gov) were searched from inception through March 1, 2020. Study Selection: Phase II/III RCTs evaluating the use of ICIs were eligible for inclusion. Unpublished trials were excluded from the analysis. Data Extraction and Synthesis: Two investigators independently performed screening of trials using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. NAEs were recorded for each arm. Data were pooled using a random-effects model. Main Outcomes and Measures: The risk of NAEs with ICI use compared with any drug regimen, cytotoxic chemotherapy, and placebo. Results: A total 39 trials including 23 705 patients were analyzed (16 135 [68.0%] men, 7866 [33.1%] White). The overall risk of a NAE was lower in the ICI group (risk ratio [RR], 0.59; 95% CI, 0.45-0.77) and in the subgroup of RCTs comparing ICI use with chemotherapy (RR, 0.22; 95% CI, 0.13-0.39). In the subgroup of RCTs comparing ICI with placebo, the overall risk of NAE was significantly higher in the ICI group (RR, 1.57; 95% CI, 1.30-1.89). Peripheral neuropathy (RR, 0.30; 95% CI, 0.17-0.51) and dysgeusia (RR, 0.41; 95% CI, 0.27-0.63) were significantly lower in the ICI group. Headache was more common with the use of ICIs (RR, 1.32; 95% CI, 1.10-1.59). In the subgroup analysis of RCTs comparing ICI use with chemotherapy, peripheral neuropathy (RR, 0.09; 95% CI, 0.05-0.17), dysgeusia (RR, 0.42; 95% CI, 0.21-0.85), and paresthesia (RR, 0.29; 95% CI, 0.13-0.67) were significantly lower in the ICI group. RCTs comparing ICIs with placebo showed a higher risk of headache with ICI use (RR, 1.63; 95%, CI, 1.32-2.02). Conclusions and Relevance: Results of this meta-analysis suggest that the overall risk of NAEs, peripheral neuropathy, and dysgeusia is lower with the use of ICI. When compared with chemotherapy, the overall risk of NAE, peripheral neuropathy, paresthesia, and dysgeusia was lower with ICI use; however, when compared with placebo, the risk of NAEs is higher with the use of ICI.

Prognostic Value of Neutrophil-lymphocyte Ratio in Patients with Severe Alcoholic Hepatitis.

Background Prednisolone is considered the cornerstone treatment for severe alcoholic hepatitis (AH). However, its use is limited by the increased risk of infection in an already immunocompromised patient population. Among patients with severe AH, there exists a group of non-responders who do not benefit from prednisolone therapy. Day-4 Lille score is a widely employed prognostic model used to identify this non-responder subgroup. The present study evaluates the prognostic ability of the inflammatory marker, the neutrophil-lymphocyte ratio (NLR), as a stand-alone model and in conjunction with the day-4 Lille score. Methods We retrospectively reviewed the electronic medical records of patients diagnosed with AH. Demographic and biochemical data at diagnosis were collected to calculate Maddrey's discriminant function (MDF) and model for end-stage liver disease (MELD) score upon admission and also on day 4. Receiver operating characteristic (ROC) curves were plotted for day-4 NLR and day-4 Lille score for prediction of 90-day mortality, and optimal cut-off values were determined. Patients were then subcategorized into groups based on the generated optimal cut-off values. Categorization was validated by comparing the mortality rate in each group with the chi-squared test. We then performed a multivariate analysis for prediction of 90-day mortality using day-4 Lille score and day-4 NLR, constructing a new prediction score based on the odds ratio (OR). The ROC curve of the new score was plotted and the area under a curve (AUC) was reported and compared with previously validated scores. Results Our analysis demonstrated that both day-4 NLR and Lille score individually predicted 90-day mortality with statistical significance (p: 0.049, p: <0.001, respectively). The ROC analysis of day-4 Lille score for the prediction of 90-day mortality revealed an AUC of 0.819 with an optimal cut-off value of 0.45 (sensitivity: 83.3%, specificity: 76.1%). Day-4 NLR had an AUC of 0.756 with an optimal cut-off value of 12.3 (sensitivity: 66.7%, specificity: 78.1%) The combined day-Lille-NLR model with a cut-off of 0.55 had an AUC of .889, which was higher than day-4 Lille score and NLR independently. Conclusion Day-4 NLR is an easily assessed prognostic model of mortality in alcoholic hepatitis. However, it often underperforms relative to day-4 Lille score. Combining these two models to create a "modified" Lille score adds increased performance characteristics to the prediction of outcomes/mortality. The "modified" Lille score presented in this study can be used to further cut down the number of non-responders who are often forced to undergo costly and potentially harmful treatment courses.

HIV-associated Non-small-cell Lung Cancer with Rearrangement of the Anaplastic Lymphoma Kinase Gene: A Report of Two Patients.

Non-small-cell lung cancer (NSCLC) is the most common non-AIDS defining cancer in patients infected with HIV and has the highest mortality rate among all cancers in this patient population. Treatment of NSCLC in HIV-positive patients is similar to that in HIV-negative patients, but less is known about the molecular characteristics of NSCLC in HIV-positive patients. This report describes two patients with HIV-associated NSCLC and rearrangements of the anaplastic lymphoma kinase (ALK) gene. The disease followed an indolent course in both patients.