scholarly journals Towards intervention development to increase the uptake of COVID-19 vaccination among those at high risk: outlining evidence-based and theoretically informed future intervention content

2020 ◽  
Author(s):  
Lynn Williams ◽  
Allyson J. Gallant ◽  
Susan Rasmussen ◽  
Louise A. Brown Nicholls ◽  
Nicola Cogan ◽  
...  
Keyword(s):  
High Risk ◽  
Mass Media ◽  
Behaviour Change ◽  
Barriers And Facilitators ◽  
Vaccine Uptake ◽  
Free Text ◽  
List Type ◽  
Environmental Consequences ◽  
To Receive ◽  
Media Interventions

AbstractObjectivesDevelopment of a vaccine against COVID-19 will be key to controlling the pandemic. We need to understand the barriers and facilitators to receiving a future COVID-19 vaccine so that we can provide recommendations for the design of interventions aimed at maximising vaccine uptake by the public.DesignCross-sectional survey with ‘high-risk’ individuals (older adults aged 65+ and patients with chronic respiratory disease).MethodsDuring the UK’s early April 2020 ‘lockdown’ period, participants (N=527; mean age = 59.5 years) completed an online questionnaire assessing willingness to receive a COVID-19 vaccine, perceptions of COVID-19, and intention to receive other vaccinations. The questionnaire included a free text response (n=502) to examine barriers and facilitators to uptake. The Behaviour Change Wheel informed the analysis of these responses, which were coded to the Theoretical Domains Framework (TDF). Behaviour change techniques (BCTs) were identified.ResultsEighty-six percent of respondents want to receive a COVID-19 vaccine. This was positively correlated with the perception that COVID-19 will continue for a long time, and negatively associated with the perception that the media has over-exaggerated the risk. The majority of barriers and facilitators could be mapped onto the ‘beliefs about consequences’ TDF domain, with themes relating to personal health, health consequences to others, concerns of vaccine safety, and severity of COVID-19.ConclusionsWillingness to receive a COVID-19 vaccination is currently high among high-risk individuals. Mass media interventions aimed at maximising vaccine uptake should utilise the BCTs of information about health, emotional, social and environmental consequences, and salience of consequences.Statement of ContributionWhat is already known on this subject?Uptake of a vaccine for COVID-19 will be vital for controlling the pandemic, but the success of this strategy relies on public acceptance of the vaccine.Uptake of vaccinations and public confidence in vaccines has been falling in recent years.Evidence suggests that 26% of the French population would not want to receive a COVID-19 vaccination.What does this study add?This study found that 86% of our sample of high-risk participants in the UK are willing to receive a future vaccine for COVID-19.This study showed that perceived barriers and facilitators to uptake of the COVID-19 vaccination concentrated on the ‘beliefs about consequences’ TDF domain.This study suggests that the content of mass media interventions to improve vaccine uptake should focus on the BCTs of information about health, emotional, social and environmental consequences, and salience of consequences. These techniques should be pitched in relation to both self and, most importantly, to others.

scholarly journals Attitudes towards vaccines and intention to vaccinate against COVID-19: Implications for public health communications in Australia

2021 ◽  
Author(s):  
Joanne Enticott ◽  
Jaskirath Gill ◽  
Simon Bacon ◽  
Kim Lavoie ◽  
Dan Epstein ◽  
...  
Keyword(s):  
Public Health ◽  
Socioeconomic Status ◽  
High Risk ◽  
Vaccine Uptake ◽  
List Type ◽  
Social Distancing ◽  
Knowing That ◽  
Vaccine Confidence ◽  
To Receive ◽  
Intent To Continue

AbstractObjectiveTo examine SARS-CoV-2 vaccine confidence, attitudes and intentions in Australian adults.MethodsNationwide survey in February-March 2021 of adults representative across sex, age and location. Vaccine uptake and a range of putative drivers of uptake, including vaccine confidence, socioeconomic status, and sources of trust, were examined using logistic and Bayesian regressions for vaccines generally and for SARS-CoV-2 vaccines.ResultsOverall 1,166 surveys were collected from participants aged 18-90 years (mean 52, SD of 19). Seventy-eight percent reported being likely to receive a vaccine against COVID-19. Higher SARS-CoV-2 vaccine intentions were associated with: increasing age (OR: 1.04 95%CI [1.03-1.044]), being male (OR: 1.37, 95% CI [1.08 – 1.72]), residing in the least disadvantaged area quintile (OR: 2.27 95%CI [1.53 – 3.37]) and a self-perceived high risk of getting COVID-19 (OR: 1.52 95% CI [1.08 – 2.14]). However, 72% of participants did not believe that they were at a high risk of getting COVID-19. Findings regarding vaccines in general were similar except there were no sex differences. For both the SARS-CoV-2 vaccine and vaccines in general, there were no differences in intentions to vaccinate as a function of education level, perceived income level, and rurality. Knowing that the vaccine is safe and effective, and that getting vaccinated will protect others, trusting the company that made it and getting vaccination recommended by a doctor were reported to influence a large proportion of the study cohort to uptake the SARS-CoV-2 vaccine. Seventy-eight percent reported the intent to continue engaging in virus-protecting behaviours (mask wearing, social distancing etc.) post-vaccine.ConclusionsSeventy-eight percent of Australians are likely to receive a SARS-CoV-2 vaccine. Key influencing factors identified in this study (e.g. knowing that the vaccine is safe and effective, getting a doctor’s recommendation to get vaccinated) can be used to inform public health messaging to enhance vaccination rates.Strengths and limitations of this studyThis research captured a large, representative sample of the adult Australian population across age, sex, location, and socioeconomic status.We have self-reported Australian uptake intentions and attitudes on general vaccines and COVID-19 vaccine, and intent to continue engaging in virus-protecting behaviours (mask wearing, social distancing etc.) post SARS-CoV-2 vaccine.We examine a range of drivers and factors that may influence intent to get the SARS-CoV-2 vaccine uptake, including vaccine confidence, demographics and socioeconomic status.The survey is based on established behavioural theories, and is the Australian arm of the international iCARE survey which to date has collected global comparative information from over 90,000 respondents in 140 countries.Our survey was only available in English, which may have led to an underrepresentation of ethnic groups, and participation was voluntary, so our sample may be prone to selection bias from those with more interest or engagement in COVID-19.

scholarly journals When to be vaccinated? What to consider? Modelling decision-making and time preference for COVID-19 vaccine through a conjoint experiment approach

2021 ◽  
Author(s):  
Samson W.H. Yuen ◽  
Ricci P.H. Yue ◽  
Bobo H.P. Lau ◽  
Siu Man Ng ◽  
Cecelia L.W. Chan
Keyword(s):  
Decision Making ◽  
Side Effects ◽  
High Risk ◽  
Head Start ◽  
Time Preference ◽  
Vaccine Uptake ◽  
Vaccination Programs ◽  
Conjoint Experiment ◽  
To Receive ◽  
New Vaccines

How do citizens choose COVID-19 vaccines, and when do they wish to be vaccinated? A choice-based conjoint experiment was fielded in Hong Kong to examine factors that shape citizens preference toward COVID-19 vaccines and their time preference to be vaccinated, which is overlooked in extant literature. Results suggest people are most concerned about vaccines efficacy and severe side-effects, and that cash incentives are not useful in enhancing vaccine appeal. The majority of respondents show low intention for immediate vaccination, and many of them want to delay their vaccination. Further analysis shows that their time preference is shaped more by respondent characteristics than vaccine attributes. In particular, confidence in the vaccine, trust in government, and working in high-risk professions are associated with earlier timing for vaccine uptake. Meanwhile, forced COVID testing would delay vaccination. The findings offer a novel view in understanding how people decide whether and when to receive new vaccines, which have pivotal implications for a head start of any mass vaccination programs.

scholarly journals Barriers and enablers to influenza vaccination uptake in adults with chronic respiratory conditions: Applying the behaviour change wheel to specify multi-levelled tailored intervention content

2020 ◽  
Author(s):  
Allyson J Gallant ◽  
Paul Flowers ◽  
Karen Deakin ◽  
Nicola Cogan ◽  
Susan Rasmussen ◽  
...  
Keyword(s):  
Influenza Vaccination ◽  
Behaviour Change ◽  
Vaccine Uptake ◽  
List Type ◽  
Factors Affecting ◽  
Vaccination Uptake ◽  
Barriers And Enablers ◽  
Behaviour Change Wheel ◽  
Intervention Content ◽  
Multi Level

AbstractObjectivesTo specify future intervention content to enhance influenza vaccination uptake using the Behaviour Change Wheel (BCW).DesignCross-sectional, multi-modal data collection and subsequent behaviourally informed analysis and expert stakeholder engagement.MethodsContent analysis was initially used to identify barriers and enablers to influenza vaccination from nine semi-structured focus groups, 21 individual interviews and 101 open-ended survey responses. Subsequently, the Theoretical Domains Framework (TDF) and the BCW were used to specify evidence-based and theoretically-informed future intervention content in the form of preliminary recommendations. Finally, drawing on the APEASE criteria, expert stakeholders refined our recommendations to yield a range of multi-levelled potentially actionable ideas.ResultsThe TDF domain of ‘Beliefs about Consequences’ was the most frequently mapped domain with themes relating to ‘perceptions of side effects (barrier)’ and ‘feeling protected from catching flu (enabler)’. The next most important domain was ‘Environmental Context and Resources’ with themes relating to ‘time constraints (barrier)’ and ‘receiving reminders to vaccinate (enabler)’. Next, ‘Social Influences’ was identified with themes relating to ‘encouragement from others (enabler)’, followed by ‘Emotion’ with themes relating to ‘fear of needles (barrier)’. These factors mapped to seven of the nine intervention functions and 22 identified behaviour change techniques (BCTs). Stakeholders reduced an initial 26 recommendations to 21.ConclusionsOur comprehensive analyses showed that the factors affecting vaccine uptake were multifaceted and multileveled. The study suggested a suite of complementary multi-level intervention components may usefully be combined to enhance vaccination uptake involving a range of diverse actors, intervention recipients and settings.Statement of ContributionWhat is already known on this subject?Uptake of the influenza vaccination in those with an “at-risk” health condition is low and has been decreasing year on year.The reasons for vaccine hesitancy are complex and involve psychological, social and contextual factors.There is a lack of theory-based intervention content aimed at increasing influenza vaccination uptake.What does this study add?This study showed that the factors affecting vaccine uptake were multifaceted and multileveled. They could be theorised as relating to the TDF domains of ‘Beliefs about Consequences’, ‘Environmental Context and Resources’, ‘Social Influences’ and ‘Emotion’.With the help of key stakeholders the study suggested a suite of complementary multi-level intervention components may be most useful to enhance vaccination compliance involving a range of diverse actors, intervention recipients and settings.Mass and social media interventions, and interactions between recipients and healthcare providers should include clear and concise information about vaccine side-effects and directly address misinformation. Community-based vaccination delivery methods should be enhanced by modifying traditional and adopting novel approaches.

scholarly journals A mega-aggregation framework synthesis of the barriers and facilitators to linkage, adherence to ART and retention in care among people living with HIV

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Lynn Hendricks ◽  
Ingrid Eshun-Wilson ◽  
Anke Rohwer
Keyword(s):  
Behaviour Change ◽  
Systematic Reviews ◽  
Methodological Quality ◽  
Antiretroviral Treatment ◽  
Critical Appraisal ◽  
Data Extraction ◽  
Retention In Care ◽  
Barriers And Facilitators ◽  
Change Model ◽  
Qualitative Evidence

Abstract Background People living with human immunodeficiency virus (PLHIV) struggle with the challenges of living with a chronic disease and integrating antiretroviral treatment (ART) and care into their daily lives. The aims of this study were as follows: (1) to undertake the first mega-aggregation of qualitative evidence syntheses using the methods of framework synthesis and (2) make sense of existing qualitative evidence syntheses that explore the barriers and facilitators of adherence to antiretroviral treatment, linkage to care and retention in care for PLHIV to identify research gaps. Methods We conducted a comprehensive search and did all screening, data extraction and critical appraisal independently and in duplicate. We used the Kaufman HIV Behaviour Change model (Kaufman et al., 2014) as a framework to synthesise the findings using the mega-aggregative framework synthesis approach, which consists of 8 steps: (1) identify a clearly defined review question and objectives, (2) identify a theoretical framework or model, (3) decide on criteria for considering reviews for inclusion, (4) conduct searching and screening, (5) conduct quality appraisal of the included studies, (6) data extraction and categorisation, (7) present and synthesise the findings, and (8) transparent reporting. We evaluated systematic reviews up to July 2018 and assessed methodological quality, across reviews, using the Joanna Briggs Institute Critical Appraisal Checklist for Systematic Reviews. Results We included 33 systematic reviews from low, middle- and high-income countries, which reported on 1,111,964 PLHIV. The methodological quality of included reviews varied considerably. We identified 544 unique third-order concepts from the included systematic reviews, which were reclassified into 45 fourth-order themes within the individual, interpersonal, community, institutional and structural levels of the Kaufman HIV Behaviour Change model. We found that the main influencers of linkage, adherence and retention behaviours were psychosocial and personal characteristics—perceptions of ART, desires, fears, experiences of HIV and ART, coping strategies and mental health issues—interwoven with other factors on the interpersonal, community, institutional and structural level. Using this approach, we found interdependence between factors influencing ART linkage, retention and adherence and identified the need for qualitative evidence that explores, in greater depth, the complex relationships between structural factors and adherence, sociodemographic factors such as community violence and retention, and the experiences of growing up with HIV in low- and middle-income countries—specifically in children, youth, women and key populations. Conclusions This is the first mega-aggregation framework synthesis, or synthesis of qualitative evidence syntheses using the methods of framework synthesis at the overview level. We found the novel method to be a transparent and efficient method for assessing the quality and making sense of existing qualitative systematic reviews. Systematic review registration The protocol of this overview was registered on PROSPERO (CRD42017078155) on 17 December 2017.

scholarly journals Willingness to Receive the COVID-19 and Seasonal Influenza Vaccines among the Saudi Population and Vaccine Uptake During the Initial Stage of the National Vaccination Campaign: A Cross-Sectional Survey

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 765
Author(s):  
Amel Ahmed Fayed ◽  
Abeer Salem Al Shahrani ◽  
Leenah Tawfiq Almanea ◽  
Nardeen Ibrahim Alsweed ◽  
Layla Mohammed Almarzoug ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Perceived Risk ◽  
Online Survey ◽  
Seasonal Influenza ◽  
Vaccination Campaign ◽  
Vaccine Uptake ◽  
Influenza Vaccines ◽  
Vaccine Hesitancy ◽  
Cross Sectional ◽  
To Receive

This study aimed to assess the willingness to receive the coronavirus disease 2019 (COVID-19) and seasonal influenza vaccines and vaccine uptake during the early stage of the national vaccination campaign in Saudi Arabia. A cross-sectional online survey was conducted among adult Saudis between 20 January and 20 March 2021. The questionnaire addressed vaccine hesitancy, perceived risk, willingness, and vaccine uptake. Approximately 39% of the participants expressed vaccine hesitancy, and 29.8% and 24% felt highly vulnerable to contracting COVID-19 and seasonal influenza, respectively. The majority (59.5%) were willing to receive the COVID-19 vaccine, although only 31.7% were willing to receive the flu vaccine. Adjusted analysis showed that vaccine hesitancy (OR 0.34, 95% CI 0.27–0.43) and the perception of being at high risk (OR 2.78, 95% CI 1.68–4.60) independently affected the intention to be vaccinated. Vaccine hesitancy was similar among those who were willing to be vaccinated (29.8%) and those who had already been vaccinated (33.1%). The perceived risk was significantly higher among those who had been vaccinated (48.1%) than among those who were willing to be vaccinated but had not yet been vaccinated (29.1%). In conclusion, the acceptance of the COVID-19 vaccine in Saudi Arabia is high. Saudis who received the vaccine had a similar level of vaccine hesitancy and a higher level of perceived risk.

scholarly journals How does participation in a voluntary prize exam affect medical students’ knowledge and interest in ENT, plastic surgery, ophthalmology and dermatology?

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Razan Nour ◽  
Kerry Jobling ◽  
Alasdair Mayer ◽  
Salma Babikir
Keyword(s):  
Medical Students ◽  
Plastic Surgery ◽  
Pilot Project ◽  
Junior Doctors ◽  
Free Text ◽  
Medical Specialties ◽  
Spare Time ◽  
Before And After ◽  
To Receive ◽  
Interest And Knowledge

Abstract Background Otolaryngology (ENT), plastic surgery, ophthalmology and dermatology are medical specialties which tend to receive less coverage in UK medical school curricula compared to larger, generalist specialties. As a result, there are fewer opportunities for medical students to learn and to cultivate an interest. There are numerous papers that report concerns about junior doctors’ ability to manage conditions within these specialties, which may jeopardise patient safety. The aim of our pilot project was to increase medical students’ interest and knowledge of ENT, plastic surgery, ophthalmology and dermatology. In addition to describing our project, we present and discuss literature on UK undergraduate education in these specialties and its impact on preparedness of junior doctors and future career choices. Methods One hundred twelve final year medical students at Newcastle University were invited to take part in a voluntary two-part (written and clinical) exam, in which prizes could be won and all participants would receive a certificate of participation. We distributed two online surveys to the students, one administered before the exam and one afterwards. Data was collected regarding the students’ motivation for entering the prize exam and the students’ baseline interest and knowledge in these specialties before and after the prize exam. Free-text responses were collected about the students’ opinion of the project and whether participation was beneficial. Results Sixteen students participated in the exam. There was a statistically significant increase in the students’ knowledge in ENT (p < 0.000), plastic surgery (p < 0.000), ophthalmology (p < 0.028) and dermatology (p < 0.012) after participation in the exam, but not in their interest levels. ENT was the preferred specialty of our cohort. The students reported that they found participation beneficial to their learning, particularly receiving exam feedback and explanations to exam questions. Conclusions This pilot project was a useful intervention in increasing medical students’ knowledge in these specialties, but not in their levels of interest. It also demonstrates that medical students are willing to participate in voluntary initiatives (in their spare time) to gain more learning opportunities and that medical students value timely exam feedback to guide their revision.

scholarly journals Perceptions of Seasonal Influenza Vaccine Among U.S. Army Civilians and Dependents in the Kaiserslautern Military Community: A Mixed-Methods Survey

2021 ◽  
Author(s):  
Veronica M Burns ◽  
Fritz M Castillo ◽  
Rodney L Coldren ◽  
Trisha Prosser ◽  
Renee L Howell ◽  
...  
Keyword(s):  
Online Survey ◽  
Seasonal Influenza ◽  
Medical Center ◽  
Vaccine Uptake ◽  
Free Text ◽  
Chi Square ◽  
Military Health ◽  
Influenza Outbreak ◽  
Flu Vaccination ◽  
Flu Vaccine

ABSTRACT Introduction Influenza is a globally occurring viral respiratory infection that can lead to hospitalizations and death. An influenza outbreak can interfere with combat readiness in a military setting, as the infection can incapacitate soldiers. Vaccination remains the most effective tool to prevent and mitigate seasonal influenza. Although influenza vaccinations for U.S. Army soldiers can be monitored through military health systems, those systems cannot capture DoD civilians and Army dependents who may not use military health services. This study aims to gauge flu vaccine uptake and perceptions in U.S. Army civilians and dependents. Materials and Methods An online survey was e-mailed to civilian and dependent enrollees of Landstuhl Regional Medical Center. The survey contained 24 questions pertaining to demographics, vaccine history, history of the flu, and beliefs toward vaccines. Chi-square tests, t-tests, and logistic regressions were performed to investigate the association between demographic, behavior, and belief factors with vaccine uptake. Free-text answers were coded and categorized by themes. Results Over 70% of respondents were vaccinated for the flu. There were differences between vaccinated and unvaccinated respondents regarding their perceptions of barriers to vaccination, benefits of the flu vaccine, severity of flu symptoms, and personal risk of getting ill with the flu. After controlling for confounders, flu vaccination in the previous season and healthcare worker status were associated with increased vaccine uptake, while perceived barriers to influenza vaccination were associated with decreased vaccine uptake. Conclusions Flu vaccine uptake may be increased by increasing access to vaccination, promoting vaccination and addressing concerns at the provider level, and engaging positively framed public messaging. Increasing flu vaccine uptake is of particular importance as the flu season approaches during the COVID-19 (Coronavirus disease 2019) pandemic.

scholarly journals Using the Theoretical Domains Framework to investigate clinicians’ behavioural determinants of antimicrobial prescribing in Qatar

2021 ◽  
Vol 29 (Supplement_1) ◽  
pp. i20-i22
Author(s):  
H Talkhan ◽  
D Stewart ◽  
T McIntosh ◽  
H Ziglam ◽  
P V Abdulrouf ◽  
...  
Keyword(s):  
Systematic Review ◽  
Scale Score ◽  
Behaviour Change ◽  
Theoretical Domains Framework ◽  
Free Text ◽  
Behaviour Change Interventions ◽  
Antimicrobial Prescribing ◽  
Behavioural Determinants ◽  
Inferential Analysis ◽  
Determinants Of Implementation

Abstract Introduction A recent systematic review by Talkhan et al demonstrated the need for theoretically based behaviour change interventions in this area. [1] For development of such complex interventions, emphasis should be placed on using theory to systematically identify behavioural determinants of antimicrobial prescribing. Aim To identify and quantify clinicians’ behavioural determinants of antimicrobial prescribing in Qatar. Methods This cross-sectional survey is part of a multi-phase explanatory, sequential mixed methods PhD project in Qatar. Questionnaires were distributed (online and paper based) to all doctors (~4,000) and pharmacists (~400) within Hamad Medical Corporation (HMC, the main healthcare provider). The questionnaire was developed with reference to the Determinants of Implementation Behaviour Questionnaire (a generic questionnaire derived from the 14 theoretical domains of the Theoretical Domains Framework, TDF). [2] Each item was presented as a 5-point Likert scale (scored 5=Strongly agree to 1=Strongly disagree). Personal and practice demographics were also collected for data contextualisation. The draft questionnaire was reviewed for face/content validity by an expert panel of six researchers in Qatar and the UK with experience in the use of the TDF, followed by ‘Think aloud’ testing and piloting. Analysis investigated the behavioural determinants and influential factors through descriptive, principal component analysis (PCA) and inferential analysis. Ethics approval was granted from a UK university and HMC. Results In total, 535 responses were received, 339 (63.4%) from doctors and 196 (36.6%) from pharmacists. Respondents were predominantly male, 346 (64.7%). Just over half (n=285, 53.3%) had ≤ 5 years’ experience as health professionals. PCA showed a three component (C) solution with components incorporating a number of questionnaire items labelled: ‘Guidelines compliance’ (C1 with 8 items), ‘Influences on prescribing’ (C2 with 7 items) and ‘Self-efficacy’ (C3 with 5 items) in prescribing/recommendation activity. A scale score for each respondent was calculated through summation of Likert scores for the relevant questionnaire items within each component. These scales had high internal reliability (Cronbach’s alpha all &gt;0.7) showing consistency in response between component items indicating statistical appropriateness for developing scales. The median score (possible scale range, midpoint) for each scale was C1, 32 (8 to 40, 24), C2, 26 (7 to 35, 21) and C3, 20, (5 to 25, 15). By way of example Table 1 shows levels of agreement for items in C2. This shows lower levels of agreement than C1 scale with the median scale score (26) closer to the midpoint (21) indicating that respondents had less positive views. Inferential analysis using these scale scores and free text analysis is in progress. Conclusion A theoretical basis was used throughout providing insights to behavioural determinants for the development of a theory-based behaviour change intervention. Preliminary results suggest that social influences, staff development and quality monitoring may be useful targets for behaviour change interventions to improve antimicrobial prescribing practice. Limitations include potential social desirability bias and focus on one healthcare organisation/country in the Middle East which may limit generalisability of findings. More in-depth exploration is required to select and test appropriate linked theory-based behaviour change techniques. References 1. Talkhan H, Stewart D, McIntosh T, Ziglam H Palli Valapila, A; Moza Sulaiman H, Diab M, Cunningham S. The use of theory in the development and evalu​ation of behaviour change interventions to improve antimicrobial prescribing: a systematic review. J Antimicrob Chemother. 2020;75(9):2394–2410, Available from https://doi.org/10.1093/jac/dkaa154 [Accessed 12 Oct 2020]. 2. Huijg JM, Gebhardt WA, Dusseldorp E, Verheijden MW, van der Zouwe N, Middelkoop BJ, Crone MR. Measuring determinants of implementation behaviour: psychometric properties of a questionnaire based on the Theoretical Domains Framework. Implement. Sci. 2014;9(1):33.

303 Phase II trial of neoadjuvant nivolumab (Nivo) and intra-tumoral (IT) CMP-001 in high-risk resectable melanoma (Neo-C-Nivo): final results

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A330-A330
Author(s):  
Diwakar Davar ◽  
Arivarasan Karunamurthy ◽  
Douglas Hartman ◽  
Richelle DeBlasio ◽  
Joe-Marc Chauvin ◽  
...  
Keyword(s):  
T Cells ◽  
High Risk ◽  
Cd8 T Cells ◽  
Advanced Melanoma ◽  
Pathologic Response ◽  
Type I ◽  
List Type ◽  
Cell Lung Carcinoma ◽  
Radiographic Response ◽  
Pathologic Features

BackgroundNeoadjuvant PD-1 blockade produces major pathological responses (MPR) in ~30% of patients (pts) with high-risk resectable melanoma (MEL) with durable relapse-free benefit, and increased circulating activated CD8+ T cells.1 2 CMP-001 is a type A CpG packaged within a virus-like particle that activates tumor-associated plasmacytoid dendritic cells (pDC) via TLR9 inducing type I interferons and anti-tumor CD8+ T cells. CMP-001/pembrolizumab produces durable anti-tumor responses in PD-1 refractory melanoma.3 We previously reported preliminary evidence of efficacy of neoadjuvant IT CMP/Nivo in high-risk resectable MEL; and herein present final results on 30 evaluable patients.Methods30 pts with stage III B/C/D MEL were enrolled. Pre-operatively, CMP-001 was dosed at 5 mg subcutaneous (SC, 1st), then 10 mg IT (2nd-7th) weekly; Nivo was dosed 240 mg q2 weeks for 3 doses – both agents given for 7 weeks. Post-operatively, Nivo was dosed 480 mg q4 weeks with CMP-001 5 mg q4 weeks SC for 48 weeks. Primary endpoints included major pathologic response rate (MPR), and incidence of dose-limiting toxicities (DLT). Secondary endpoints were radiographic response, relapse-free survival (RFS) and overall survival (OS). Pathological response was scored blinded by pathologists based on residual volume of tumor (RVT) using prior specified cutoffs:4 60% (complete response, pCR); 0%<rvt<rvt50% (non-response, pNR). Radiographic response was assessed using RECIST v1.1. Sequential blood draws and tumor biopsies were collected and analyzed for CD8+ T cell infiltrate (TIL), multiparameter flow cytometry (MFC) and multiplex immunofluorescence (mIF).Results30 pts with regionally advanced MEL were enrolled, of stages IIIB (57%), IIIC (37%), IIID (7%). 29/30 (97%) of pts completed 7 weeks of neoadjuvant Nivo/CMP; while 1 pt had a delay in surgery related to a pre-operative infection unrelated to therapy. No DLTs were reported; grade 3/4 irAE were reported in 3 pts (11%) leading to CMP-001 discontinuation in 2 pts (7%). Radiographic responses were seen in 13 pts (43%), while 9 pts (30%) had stable disease and 8 pts (27%) had progressive disease. Pathological responses (RVT <50%) were seen in 70% of pts: pCR 15 (50%), pMR 3 (10%), 3 pPR (10%); only 9 (30%) had pNR. Pathological responders (pCR/pMR) had increased CD8+ TIL and CD303+ pDC intra-tumorally by mIF; and peripherally activated PD1+/Ki67+ CD8+ T cells by MFC.ConclusionsNeoadjuvant CMP/Nivo has acceptable toxicity and promising efficacy. MPR is 60% in 30 pts. 1-year RFS was 82% (all pts) and 89% (among those with pCR/pMR); median RFS is 9 months (among pNR/pPR) and not reached (among pCR/pMR). Response is associated with evidence of immune activation intra-tumorally and peripherally. IT CMP001 increases clinical efficacy of PD-1 blockade with minimal additional toxicity in pts with regionally advanced MEL. Further study of this combination in high-risk resectable MEL is planned.AcknowledgementsWe thank Dr. Jagjit Singh and the pathology grossing room staff for their assistance and Checkmate Pharmaceuticals for funding and CMP-001.Trial RegistrationClinical trial information: NCT03618641Ethics ApprovalThe study was approved by University of Pittsburgh’s Institutional Review Board, approval number MOD19040237-002.ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.ReferencesAmaria RN, Reddy SM, Tawbi HA, et al. Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma. Nat Med 2018. Nov;24(11):1649–1654.Huang AC, Orlowski RJ, Xu X, et al. A single dose of neoadjuvant PD-1 blockade predicts clinical outcomes in resectable melanoma. Nat Med 2019. Mar;25(3):454–461. doi: 10.1038/s41591-019-0357-y.Milhem M, Gonzales R, Medina T, et al. Abstract CT144: Intratumoral toll-like receptor 9 (TLR9) agonist, CMP-001, in combination with pembrolizumab can reverse resistance to PD-1 inhibition in a phase Ib trial in subjects with advanced melanoma. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14–18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract CT144.Tetzlaff MT, Messina JL, Stein JE, et al. Pathological assessment of resection specimens after neoadjuvant therapy for metastatic melanoma. Ann Oncol 2018. Aug 1;29(8):1861–1868.Cottrell TR, Thompson ED, Forde PM, et al. Pathologic features of response to neoadjuvant anti-PD-1 in resected non-small-cell lung carcinoma: a proposal for quantitative immune-related pathologic response criteria (irPRC). Ann Oncol 2018 Aug 1;29(8):1853–1860. doi: 10.1093/annonc/mdy218.Stein JE, Soni A, Danilova L, et al. Major pathologic response on biopsy (MPRbx) in patients with advanced melanoma treated with anti-PD-1: evidence for an early, on-therapy biomarker of response. Ann Oncol 2019 Apr 1;30(4):589–596. doi: 10.1093/annonc/mdz019.

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