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

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18763-e18763
Author(s):  
Naga Malleswari Vutukuri ◽  
Calette Corcoran ◽  
Jill Comeau ◽  
Elizabeth Stephenson ◽  
Kavitha Beedupalli ◽  
...  
Keyword(s):  
Adverse Events ◽  
Influenza Vaccine ◽  
Influenza Vaccination ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Secondary Outcome ◽  
Number Of Patients ◽  
Influenza Vaccinations

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

2019 ◽  
Vol 26 (3) ◽  
pp. 647-654 ◽  
Author(s):  
Morgan E Gwynn ◽  
David L DeRemer ◽  
Katherine M Saunders ◽  
Jigarkumar Parikh ◽  
Roni J Bollag ◽  
...  
Keyword(s):  
Adverse Events ◽  
Influenza Vaccine ◽  
Influenza Vaccination ◽  
Immune Checkpoint ◽  
Medical Records ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Patient Questionnaire ◽  
Immune Mediated ◽  
Increased Risk

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.

scholarly journals An Evaluation of the Use of Corticosteroids for the Management of Immune-Mediated Adverse Events in Cancer Patients Treated With Immune Checkpoint Inhibitors

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Adrian Tsui, PharmD ◽  
Linday Edmondson, PharmD, BCOP ◽  
Justin Julius, PharmD
Keyword(s):  
Adverse Events ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Retrospective Chart Review ◽  
Prescribing Practices ◽  
Immune Mediated ◽  
Number Of Patients ◽  
Secondary Endpoints

Immune checkpoint inhibitors (ICIs) have gained prominence for the treatment of a variety of malignancies. However, they are associated with the development of immune-mediated adverse events (IMAEs). Appropriate management of IMAEs and subsequent rechallenging of patients with ICI therapy remains an important area of research. The primary endpoint of this study was to evaluate the efficacy of current prescribing practices and adherence to guideline recommendations for IMAE management. The incidence of symptom resolution, number of patients reinitiated with ICI therapy, and IMAE recurrence upon ICI therapy reinitiation were explored as secondary endpoints. A retrospective chart review within the Allegheny Health Network was conducted in cancer patients treated with ICI therapy who developed a documented ICI-associated IMAE and subsequently received corticosteroid therapy. IRB approval was obtained for this study. Descriptive statistics were used to analyze both primary and secondary endpoints. The study sample was made up of 81 patients. Overall, 50 out of 81 patient cases (62%) were found to be discordant with guideline recommendations; the primary factors identified were inappropriate starting corticosteroid dosing (64%), initiation of a corticosteroid taper prior to IMAE resolution to at least grade 1 severity, and condensed corticosteroid taper (74%). The main IMAEs identified were colitis (28%), pneumonitis (27%), and skin-related inflammation (12%). 76 out of the 81 patients (94%) achieved IMAE resolution; 41 patients (54%) were rechallenged with ICI therapy, of which 14 patients (34%) developed IMAE recurrence. Future studies may focus on evaluating different immunosuppression strategies to optimize IMAE management.

Assessment of hospitalization rates for immune-related adverse events with immune checkpoint inhibitors

2020 ◽  
pp. 107815522096890
Author(s):  
Laura Nice ◽  
Ryan Bycroft ◽  
Xiaoyong Wu ◽  
Shesh N Rai ◽  
Lindsay Figg ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Median Length ◽  
Number Of Patients ◽  
Grade 3 ◽  
The Impact

Introduction Immune checkpoint inhibitors (ICIs) have become the standard of care in many cancer types. As the number of patients receiving ICIs for various cancers continues to expand, patients and practitioners should be aware of potentially severe immune-related adverse events (irAEs). Despite reports of the incidence of grade 3/4 toxicities, the proportion of patients whose symptoms were clinically severe enough to warrant hospitalization for adverse event management is unknown. Methods This single center, retrospective, observational study was designed to determine the impact of irAEs on patients and the hospital. Patients who started ICIs from May 2016 through May 2019 for melanoma or lung cancer were included. The primary outcome was incidence of hospitalization for irAE. Secondary outcomes included median length of hospitalization, time to onset of irAE, rates of hospitalization for irAE per each checkpoint inhibitor regimen, organ system affected, progression free survival, and overall survival. Results Of 384 patients with melanoma or lung cancer, 27 (7%) were hospitalized at our institution for an irAE. The most common irAE leading to hospitalization was colitis for patients with melanoma and pneumonitis for patients with lung cancer. The median length of stay across all hospitalizations was 10 days. Twenty-five patients required the use of corticosteroids while hospitalized, while eight of these patients required second line irAE treatment. For the total patient population, 34.7% experienced a grade 1/2 irAE and 13.1% experienced a grade 3/4 irAE. Conclusion Our cohort of patients experienced similar rates irAEs as reported in clinical trials and published reports.

Immortal time bias in the association between toxicity and response for immune checkpoint inhibitors: A systematic review and meta-analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15080-e15080
Author(s):  
Filippo G. Dall'Olio ◽  
Alessandro Rizzo ◽  
Veronica Mollica ◽  
Maria Massucci ◽  
Ilaria Maggio ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Prognostic Impact ◽  
Cancer Type ◽  
Landmark Analysis ◽  
Immortal Time Bias ◽  
Number Of Patients

e15080 Background: A number of studies have addressed the association between Immune related Adverse Events (IrAE) and outcome in patients treated with Immune Checkpoint Inhibitors (ICI). Only a minority of them considered the effect of immortal time bias (ITB), and results of these papers are conflicting. The aim of our meta-analysis was to assess the relationship between IrAE and outcomes for patients treated with ICIs, with a focus on ITB in weighing the role of this association. Methods: PubMed, Embase (Ovid), and Scopus were searched through January 2, 2020. Studies reporting the prognostic impact of IrAE development on outcome in advanced cancer patients treated with anti PD-1 or PD-L1.Two investigators independently extracted data from each study following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guideline. Author name, cancer type, PD-1 and PD-L1 inhibitor used, number of patients, number and type of all adverse events, presence of a landmark analysis, median OS and PFS and difference between patient with or without IrAE in terms of OS and PFS (Hazard Ratio) and ORR (Odds Ratio) were extracted. Data were pooled using a random-effects model. Main outcome were Overall Survival (OS), Progression Free Survival (PFS) and Overall Response Rate (ORR). Analysis was performed with dedicated software (R studio version 1.2.1335, metafor package). Results: A total of 29 articles comprising 7430 patients were included. 7 papers published the results of survival analysis according to landmark analysis, 2 papers published only the naïve analysis while stating that a landmark analysis resulted non significant, and the others did not perform a landmark analysis. IrAEs were associated with improved outcomes with high heterogeneity ( I2 70.8%, p < 0.001 for OS; 65.7%, p 0.002 for PFS; 62.1%, p 0.001 for ORR). When subgroup analysis was performed according to the adoption of a landmark approach, the association between IrAE and outcome remains significant for OS, PFS and ORR but the effect size was smaller ( HR 0.61 vs 0.41 for OS, ANOVA Q-test for difference between subgroup p = 0.015; HR 0.66 vs 0.47 for PFS, ANOVA Q-test p 0.029; OR 2.59 vs 6.77 for ORR, ANOVA Q-test p < 0.001) while heterogeneity was substantially reduced (I2 for papers using LM 43% for OS, p 0.115; 9.7% for PFS, p 0.355; 0.0% for ORR, p 0.556). Conclusions: Our analysis suggests a significant confounding effect of ITB as well as a real effect of IrAE development on outcome.

Immunogenicity of Influenza Vaccination in Patients with Cancer Receiving Immune Checkpoint Inhibitors

2019 ◽  
Vol 71 (2) ◽  
pp. 422-425 ◽  
Author(s):  
Bhumsuk Keam ◽  
Chang Kyung Kang ◽  
Kang Il Jun ◽  
Song Mi Moon ◽  
Koung Jin Suh ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Influenza Vaccination ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cytotoxic Chemotherapy ◽  
Cytotoxic Agents ◽  
Patients With Cancer ◽  
Influenza Vaccinations

Abstract Among prospectively enrolled adult patients with cancer receiving immune checkpoint inhibitors (ICIs; n = 46) or cytotoxic agents (n = 90), seroprotection and seroconversion rates after seasonal quadrivalent influenza vaccinations were higher with ICI than with cytotoxic chemotherapy. These results support annual influenza vaccinations for cancer patients receiving ICIs. Clinical Trials Registration clinicaltrials.gov (NCT03590808).

CLO19-031: Immune Checkpoint Inhibitors: Optimization of Pharmacy Services in Toxicity Management

2019 ◽  
Vol 17 (3.5) ◽  
pp. CLO19-031
Author(s):  
Olivia G. Fahey ◽  
Elizabeth N. Dow ◽  
Jennifer K. Piccolo ◽  
Ticiana A. Leal
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Hospital Admissions ◽  
Checkpoint Inhibitors ◽  
Emergency Department Visits ◽  
Cancer Center ◽  
Number Of Patients ◽  
Common Grade ◽  
Grade 3

Background: Use of immune checkpoint inhibitors (ICPi) in oncology continues to rapidly expand. ICPis have a unique toxicity profile and can lead to immune related adverse events (irAEs), some serious and potentially life-threatening. Early detection and appropriate treatment may limit the morbidity and mortality of irAEs and allow patients who are deriving benefit from ICPi to continue treatment. Pharmacists practicing in UW Health Carbone Cancer Center clinics are uniquely positioned to educate patients about common ICPi toxicities and ensure appropriate, early recognition and management of irAEs in collaboration with the multidisciplinary team. Methods: Within lung, melanoma, and gastrointestinal medical oncology clinics, a program was implemented involving pharmacists educating patients and families prior to the start of treatment as well as contacting patients at regular intervals to assess for any signs or symptoms of irAEs. The primary outcome is the number of patients experiencing Common Terminology Criteria for Adverse Events version 5.0 (CTCAE) grade 1 or 2 irAEs identified by a pharmacist enrolled in the program. Secondary outcomes include grade ≥ 3 irAEs identified by a pharmacist, the total number of patients enrolled in the program with any irAE, reason for discontinuation of ICPi, emergency department visits, and hospital admissions during the study period. Results: Between November 14, 2017 and October 15, 2018, a total of 81 patients were enrolled in the program with 49 of those patients still enrolled at the end of the study period. These patients experienced a total of 39 grade 1 and 13 grade 2 irAEs, of which 53.8% (n=28) were identified by pharmacists. The most common grade 1 or 2 toxicities identified by pharmacists were gastrointestinal (n=15) and dermatologic (n=6). Endocrine (n=7) and dermatologic (n=7) were the most common grade 1 or 2 irAEs identified by other providers. There were 4 grade 3 irAEs (endocrine, fatigue, liver, and pneumonitis) identified by other providers, and there were no grade 4 irAEs. Conclusion: Proactive pharmacist contact at regular intervals during ICPi treatment resulted in the early discovery of grade 1 or 2 irAEs experienced by patients. This pharmacist-driven approach may allow for earlier treatment of any toxicities experienced after ICPi treatment and reduce the rates of serious irAEs. Current efforts are focused on expanding these services to all UW Health Carbone Cancer Center clinics.

scholarly journals INfluenza Vaccine Indication During therapy with Immune checkpoint inhibitors: a multicenter prospective observational study (INVIDIa-2)

2021 ◽  
Vol 9 (5) ◽  
pp. e002619
Author(s):  
Melissa Bersanelli ◽  
Diana Giannarelli ◽  
Ugo De Giorgi ◽  
Sandro Pignata ◽  
Massimo Di Maio ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Influenza Vaccination ◽  
Advanced Cancer ◽  
Primary Endpoint ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Group Performance ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Study Results

BackgroundUntil now, no robust data supported the efficacy, safety and recommendation for influenza vaccination in patients with cancer receiving immune checkpoint inhibitors (ICIs).MethodsThe prospective multicenter observational INfluenza Vaccine Indication During therapy with Immune checkpoint inhibitors (INVIDIa-2) study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving ICIs, enrolled in 82 Italian centers from October 2019 to January 2020. The primary endpoint was the time-adjusted incidence of influenza-like illness (ILI) until April 30, 2020. Secondary endpoints regarded ILI severity and vaccine safety.ResultsThe study enrolled 1279 patients; 1188 patients were evaluable for the primary endpoint analysis. Of them, 48.9% (581) received influenza vaccination. The overall ILI incidence was 8.2% (98 patients). Vaccinated patients were significantly more frequently elderly (p<0.0001), males (p=0.004), with poor European Cooperative Oncology Group performance status (p=0.009), affected by lung cancer (p=0.01), and by other non-cancer comorbidities (p<0.0001) when compared with unvaccinated. ILI incidence was not different basing on influenza vaccination: the time-to-ILI was similar in vaccinated and unvaccinated patients (p=0.62). ILI complications were significantly less frequent for patients receiving the vaccination (11.8% vs 38.3% in unvaccinated, p=0.002). ILI-related intravenous therapies were significantly less frequent in vaccinated patients than in unvaccinated (11.8% vs 29.8%, p=0.027). ILI lethality was, respectively, 0% in vaccinated and 4.3% in unvaccinated patients. Vaccine-related adverse events were rare and mild (1.5%, grades 1–2).ConclusionThe INVIDIa-2 study results support a positive recommendation for influenza vaccination in patients with advanced cancer receiving immunotherapy.

scholarly journals Rechallenge patients with immune checkpoint inhibitors following severe immune-related adverse events: review of the literature and suggested prophylactic strategy

2020 ◽  
Vol 8 (1) ◽  
pp. e000604 ◽  
Author(s):  
John Haanen ◽  
Marc Ernstoff ◽  
Yinghong Wang ◽  
Alexander Menzies ◽  
Igor Puzanov ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Clinical Benefit ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Relevant Literature ◽  
Immune Checkpoint Blockade ◽  
Multidisciplinary Teams ◽  
Patients With Cancer ◽  
Number Of Patients

Patients with cancer who developed severe, grade 3 or 4 immune-related adverse events (irAEs) during therapy with immune checkpoint inhibitors are at risk for developing severe toxicities again on rechallenge with checkpoint inhibitors. Consequently, medical oncologists and multidisciplinary teams are hesitant to retreat in this scenario, despite the fact that a number of patients may derive clinical benefit from this approach. Balancing such clinical benefit and treatment-related toxicities for each patient is becoming increasingly challenging as more and more patients with cancer are being treated with checkpoint inhibitors. In this manuscript, we provide an extensive overview of the relevant literature on retreatment after toxicity, and suggest prophylactic approaches to minimize the risk of severe irAE following rechallenge with immune checkpoint blockade, since treatment may be lifesaving in a number of occasions.

Immune related adverse events in NSCLC patients treated with immune checkpoint therapy who received the influenza vaccination versus no vaccination.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20657-e20657
Author(s):  
Haritha G. Reddy ◽  
Taylor Mai Weis ◽  
Shannon Hough ◽  
Stephanie Daignault ◽  
Bryan J. Schneider
Keyword(s):  
Adverse Events ◽  
Influenza Vaccine ◽  
Influenza Vaccination ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Small Sample Size ◽  
Performance Status ◽  
Small Sample ◽  
Ecog Performance Status ◽  
Chi Square

e20657 Background: Influenza vaccination is recommended by the CDC for cancer patients to reduce the risk of influenza-related complications. There is concern that the incidence of immune-related adverse events (irAEs) may be greater in vaccinated patients receiving immune checkpoint inhibitors (ICPI). We sought to interrogate if influenza vaccination in patients with NSCLC receiving ICPI therapy had an increased incidence of irAEs compared to non-vaccinated patients. Methods: We conducted a single-center retrospective analysis of patients with advanced NSCLC who received PD-1 or PD-L1 inhibitor monotherapy between 3/2015 – 12/2018. Influenza immunization records from both institutional and state-wide registries were obtained from 2014 -2019. Comparisons of adverse event incidence between flu vaccinated and control patients were tested using chi-square statistics. Results: 117 patients were included in our analysis, 33 (28%) were vaccinated during ICPI therapy, 19 (58%) received quadrivalent influenza vaccine, 13 (39%) received trivalent influenza vaccine and 1 (3%) was undetermined. 22 (67%) vaccinated patients had an irAE vs 53 (63%) patients who were not vaccinated during ICPI therapy (p = 0.720). 8 (24%) vaccinated patients had an irAE leading to discontinuation of therapy vs 12 (14%) patients who were not vaccinated during ICPI therapy (p = 0.198). The most frequent irAE in both groups was fatigue 16 (48%) vs 28 (33%) (p = 0.128). Notable irAEs included colitis (0 vs 1), pneumonitis (3 vs 3), hepatitis (1 vs 4) in vaccinated patients vs without vaccine, respectively. There were no statistically significant differences in baseline demographics between both groups including age, race, gender, tumor histology or ECOG performance status. Conclusions: Our study suggests that irAEs are not significantly increased with vaccination for influenza during ICPI therapy. However, there is a slight trend toward increased incidence of irAE warranting ICPI discontinuation for which further investigation is needed. Limitations of this study include a small sample size and inability to grade irAE retrospectively.

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