Economic Evaluations of Chimeric Antigen Receptor T-Cell Therapies for Hematologic and Solid Malignancies: A Systematic Review.

OBJECTIVES: This study aimed to systematically review evidence on the cost-effectiveness of chimeric antigen receptor T-cell (CAR-T) therapies for patients with cancer. METHODS: Electronic databases were searched in October 2022 and updated in September 2023. Systematic reviews, health technology assessments, and economic evaluations that compared costs and effects of CAR-T therapy in patients with cancer were included. Two reviewers independently screened studies, extracted data, synthesized results, and critically appraised studies using the Philips checklist. Cost data were presented in 2022 US dollars. RESULTS: Our search yielded 1809 records, 47 of which were included. Most of included studies were cost-utility analysis, published between 2018 and 2023, and conducted in the United States. Tisagenlecleucel, axicabtagene ciloleucel, idecabtagene vicleucel, ciltacabtagene autoleucel, lisocabtagene maraleucel, brexucabtagene autoleucel, and relmacabtagene autoleucel were compared with various standard of care chemotherapies. The incremental cost-effectiveness ratio (ICER) for CAR-T therapies ranged from $9424 to $4 124 105 per quality-adjusted life-year (QALY) in adults and from $20 784 to $243 177 per QALY in pediatric patients. Incremental cost-effectiveness ratios were found to improve over longer time horizons or when an earlier cure point was assumed. Most studies failed to meet the Philips checklist due to a lack of head-to-head comparisons and uncertainty surrounding CAR-T costs and curative effects. CONCLUSIONS: CAR-T therapies were more expensive and generated more QALYs than comparators, but their cost-effectiveness was uncertain and dependent on patient population, cancer type, and model assumptions. This highlights the need for more nuanced economic evaluations and continued research to better understand the value of CAR-T therapies in diverse patient populations.

Reduced seasonal coronavirus incidence in high-risk population groups during the COVID-19 pandemic.

BACKGROUND: Epidemiological data on seasonal coronaviruses (sCoVs) may provide insight on transmission patterns and demographic factors that favor coronaviruses (CoVs) with greater disease severity. This study describes the incidence of CoVs in several high-risk groups in Ottawa, Canada, from October 2020 to March 2022. METHODS: Serological assays quantified IgG and IgM antibodies to SARS-CoV-2, HCoV-OC43, HCoV-NL63, HCoV-HKU1, and HCoV-229E. Incident infections were compared between four population groups: individuals exposed to children, transit users, immunocompromised, and controls. Associations between antibody prevalence indicative of natural infection and demographic variables were assessed using regression analyses. RESULTS: Transit users and those exposed to children were at no greater risk of infection compared to the control group. Fewer infections were detected in the immunocompromised group (p = .03). SARS-CoV-2 seroprevalence was greater in individuals with low income and within ethnic minorities. CONCLUSIONS: Our findings suggest that nonpharmaceutical interventions intended to reduce SAR-CoV-2 transmission protected populations at high risk of exposure. The re-emergence of sCoVs and other common respiratory viruses alongside SARS-CoV-2 may alter infection patterns and increase the risk in vulnerable populations.

Seasonal respiratory virus circulation was diminished during the COVID-19 pandemic.

BACKGROUND: Measures introduced during the COVID-19 pandemic intended to address the spread of SARS-CoV-2 may also influence the incidence of other common seasonal respiratory viruses (SRV). This evaluation reports laboratory-confirmed cases of common SRV in a well-defined region of central Canada to address this issue. METHODS: Surveillance data for common non-SARS-CoV-2 SRV in Ottawa, Canada, was provided by the Eastern Ontario Regional Laboratory Association (EORLA) reference virology lab. Weekly reports of the number of positive tests and the proportion that yielded positive results were analyzed from August 26, 2018, to January 2, 2022. RESULTS: A drastic reduction in influenza and other common SRV was observed during the 2020-2021 influenza season in the Ottawa region. Influenza was virtually undetected post-SARS-CoV-2 emergence. Rhinoviruses and enteroviruses were the only viruses that remained relatively unaffected during this period. CONCLUSIONS: We speculated that the introduction of nonpharmaceutical measures including masking to prevent SARS-CoV-2 transmission contributed to the near absence of SRV in the Ottawa region. These measures should remain a key component in addressing spikes in SRV activity and future pandemics.

Results of the Stop the Spread Ottawa (SSO) cohort study: a Canadian urban-based prospective evaluation of antibody responses and neutralisation efficiency to SARS-CoV-2 infection and vaccination.

BACKGROUND: Predictors of COVID-19 vaccine immunogenicity and the influence of prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection require elucidation. METHODS: Stop the Spread Ottawa is a prospective cohort of individuals at-risk for or who have been infected with SARS-CoV-2, initially enrolled for 10 months beginning October 2020. This cohort was enriched for public-facing workers. This analysis focuses on safety and immunogenicity of the initial two doses of COVID-19 vaccine. RESULTS: Post-vaccination data with blood specimens were available for 930 participants. 22.8% were SARS-CoV2 infected prior to the first vaccine dose. Cohort characteristics include: median age 44 (IQR: 22-56), 66.6% women, 89.0% white, 83.2% employed. 38.1% reported two or more comorbidities and 30.8% reported immune compromising condition(s). Over 95% had detectable IgG levels against the spike and receptor binding domain (RBD) 3 months post second vaccine dose. By multivariable analysis, increasing age and high-level immune compromise predicted diminishing IgG spike and RBD titres at month 3 post second dose. IgG spike and RBD titres were higher immediately post vaccination in those with SARS-CoV-2 infection prior to first vaccination and spike titres were higher at 6 months in those with wider time intervals between dose 1 and 2. IgG spike and RBD titres and neutralisation were generally similar by sex, weight and whether receiving homogeneous or heterogeneous combinations of vaccines. Common symptoms post dose 1 vaccine included fatigue (64.7%), injection site pain (47.5%), headache (27.2%), fever/chills (26.2%) and body aches (25.3%). These symptoms were similar with subsequent doses. CONCLUSION: The initial two COVID-19 vaccine doses are safe, well-tolerated and highly immunogenic across a broad spectrum of vaccine recipients including those working in public facing environments.

SARS-CoV-2 Seroprevalence in Those Utilizing Public Transportation or Working in the Transportation Industry: A Rapid Review.

Proximity and duration of social contact while working or using public transportation may increase users' risk of SARS-CoV-2 exposure. This review aims to assess evidence of an association between use of public transportation or work in the transportation industry and prevalence of SARS-CoV-2 antibodies as well as to identify factors associated with seropositivity in transit users. A literature search of major databases was conducted from December 2019 to January 2022 using key worlds including "seroprevalence", "SARS-CoV-2", and "public transit". A narrative review of included studies was completed for the following categories: those working in the transportation industry, healthcare workers relying on public transit, and population-based studies. The association between work in the transit industry and seroprevalence varied based on location, demographic characteristics, and test sensitivities. No association was found in healthcare workers. Several population-based studies indicated higher seroprevalence in those using public transit. Overall seroprevalence estimates varied based on geographic location, population demographics, study methodologies, and calendar date of assessment. However, seropositivity was consistently higher in racial minorities and low-income communities.

Cohort profile: Stop the Spread Ottawa (SSO)-a community-based prospective cohort study on antibody responses, antibody neutralisation efficiency and cellular immunity to SARS-CoV-2 infection and vaccination.

PURPOSE: To investigate the robustness and longevity of SARS-CoV-2 immune responses conferred by natural infection and vaccination among priority populations such as immunocompromised individuals and people with post-acute sequelae of COVID-19 in a prospective cohort study (Stop the Spread Ottawa-SSO) in adults living in the Ottawa region. In this paper, we describe the study design, ongoing data collection and baseline characteristics of participants. PARTICIPANTS: Since October 2020, participants who tested positive for COVID-19 (convalescents) or at high risk of exposure to the virus (under surveillance) have provided monthly blood and saliva samples over a 10-month period. As of 2 November 2021, 1026 adults had completed the baseline survey and 976 had attended baseline bloodwork. 300 participants will continue to provide bimonthly blood samples for 24 additional months (ie, total follow-up of 34 months). FINDINGS TO DATE: The median age of the baseline sample was 44 (IQR 23, range: 18-79) and just over two-thirds (n=688; 67.1%) were female. 255 participants (24.9%) had a history of COVID-19 infection confirmed by PCR and/or serology. Over 600 participants (60.0%) work in high-risk occupations (eg, healthcare, teaching and transportation). 108 participants (10.5%) reported immunocompromising conditions or treatments at baseline (eg, cancer, HIV, other immune deficiency, and/or use of immunosuppressants). FUTURE PLANS: SSO continues to yield rich research potential, given the collection of pre-vaccine baseline data and samples from the majority of participants, recruitment of diverse subgroups of interest, and a high level of participant retention and compliance with monthly sampling. The 24-month study extension will maximise opportunities to track SARS-CoV-2 immunity and vaccine efficacy, detect and characterise emerging variants, and compare subgroup humoral and cellular response robustness and persistence.