Immune-mediated adverse events following influenza vaccine in cancer patients receiving immune checkpoint inhibitors.

OBJECTIVES: The emergence of immune checkpoint inhibitors has transformed treatment paradigms for various malignancies. Patients with cancer are at increased risk of complications and hospitalizations from influenza; therefore, it is recommended that they receive inactivated influenza vaccination. However, efficacy and safety of inactivated influenza vaccination in patients receiving immune checkpoint inhibitors is uncertain. The objective of this prospective case series was to evaluate the incidence of immune-mediated adverse events (imAEs) following inactivated influenza vaccination in patients receiving immune checkpoint inhibitors. Changes in cytokine and chemokine levels were also evaluated. METHODS: Patients receiving immune checkpoint inhibitors during the 2017-2018 influenza season were eligible for study participation. Peripheral blood samples were collected prior to administration of inactivated influenza vaccine and two post-vaccination time points. Evaluation of new or worsening imAEs occurred via patient questionnaire and review of medical records for 60 days following inactivated influenza vaccination. Baseline imAEs were evaluated from review of medical records for 60 days prior to inactivated influenza vaccination. Serum cytokines and chemokines were measured using a multiplex Luminex assay. RESULTS: Twenty-four patients were enrolled in this study. Seven patients experienced any grade imAE (one patient having 2) within 60 days following inactivated influenza vaccination. The majority were Grades 1-2, including rash (n = 3), hypothyroidism, myalgia, and colitis (n = 1 each). Two patients experienced severe imAEs (grade 3 nephritis and grade 4 diabetes). No significant changes (p > 0.05) in serum cytokine or chemokine concentrations were observed. CONCLUSIONS: Although small, our study suggests that inactivated influenza vaccine may be safely administered to patients receiving immune checkpoint inhibitors. The majority of imAEs following inactivated influenza vaccination were Grades 1-2 and did not require changes in immune checkpoint inhibitor therapy.

The Emerging Role of PD-1/PD-L1-Targeting Immunotherapy in the Treatment of Metastatic Urothelial Carcinoma.

OBJECTIVE: To summarize and evaluate immunotherapy agents targeting programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) recently approved for the treatment of metastatic urothelial carcinomas (UC). DATA SOURCES: A literature review was performed using PubMed (2012 to June 2017), the American Society of Clinical Oncology abstract databases (2012 to June 2017 Annual Meetings/symposia), and the America Association for Cancer Research symposia (2012 to June 2017). A search using clinicaltrials.gov was conducted to identify studies for atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab. STUDY SELECTION AND DATA EXTRACTION: English language phase I to III studies assessing PD-1 and PD-L1 in UC were incorporated. DATA SYNTHESIS: Atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab have demonstrated clinical efficacy with tolerable toxicities in patients with metastatic UC with disease progression following platinum-based chemotherapy. Anti-PD-1/PD-L1 therapies may provide overall survival advantage; these are currently being evaluated in ongoing phase 3 studies. Greater objective response rates seem to be observed in PD-L1-positive patients versus PD-L1-negative patients, but methodologies in this assessment differ among clinical trials. The identification of biomarkers that provide greater insight into patients who positively respond to PD-1/PD-L1 therapies are needed. CONCLUSIONS: Treatment options for metastatic UC have expanded to include PD-1/PD-L1 therapies. These agents should be strongly considered as second-line therapy over single-agent chemotherapy for patients who fail or progress after platinum-based treatment.

Characterization of changes in medication complexity using a modified scoring tool.

PURPOSE: The purpose of this study was to characterize dynamic changes in medication regimen complexity over time in critically ill adults and to validate a modified version of the medication regimen complexity-intensive care unit (MRC-ICU) scoring tool. SUMMARY: A single-center, retrospective, observational chart review was conducted with a primary aim of assessing changes in medication regimen complexity over time, as measured by both the 39-item MRC-ICU scoring tool and a modified version (the mMRC-ICU) containing just 17 items. Secondary aims included validation of the mMRC-ICU and exploration of relationships between medication regimen complexity and ICU length of stay (LOS), inpatient mortality, and patient acuity. Adults admitted to a medical ICU from November 2016 through June 2017 were included. The medication regimens of a total of 130 patients were scored in order to test, modify, and validate the MRC-ICU and mMRC-ICU tools. The modified tool was validated by evaluating correlation of mMRC-ICU scores with MRC-ICU scores and with patient outcomes including patient acuity, ICU LOS, and inpatient mortality. mMRC-ICU scores were collected at 24 and 48 hours after admission and at ICU discharge to evaluate changes over time. Significant changes in medication regimen complexity over time were observed, with the highest scores observed at 24 hours after admission. CONCLUSION: Medication regimen complexity may provide valuable insights into pharmacist activity and resource allocation. Further validation of the MRC-ICU and mMRC-ICU scoring tools in other critically ill populations and at external sites is required.

Development and validation of a medication regimen complexity scoring tool for critically ill patients.

PURPOSE: The purpose of this study was to develop and validate a novel medication regimen complexity-intensive care unit (MRC-ICU) scoring tool in critically ill patients and to correlate MRC with illness severity and patient outcomes. METHODS: This study was a single-center, retrospective observational chart review of adults admitted to the medical ICU (MICU) between November 2016 and June 2017. The primary aim was the development and internal validation of the MRC-ICU scoring tool. Secondary aims included external validation of the MRC-ICU and exploration of relationships between medication regimen complexity and patient outcomes. Exclusion criteria included a length of stay of less than 24 hours in the MICU, active transfer, or hospice orders at 24 hours. A total of 130 patient medication regimens were used to test, modify, and validate the MRC-ICU tool. RESULTS: The 39-line item medication regimen complexity scoring tool was validated both internally and externally. Convergent validity was confirmed with total medications (p < 0.0001). Score discriminant validity was confirmed by lack of association with age (p = 0.1039) or sex (p = 0.7829). The MRC-ICU score was significantly associated with ICU length of stay (p = 0.0166), ICU mortality (p = 0.0193), and patient acuity (p < 0.0001). CONCLUSION: The MRC-ICU scoring tool was validated and found to correlate with length of stay, inpatient mortality, and patient acuity.