The use of pembrolizumab monotherapy for the management of head and neck squamous cell carcinoma (HNSCC) in the UK.

Pembrolizumab has received approval in the UK as first-line monotherapy for recurrent and/or metastatic HNSCC (R/M HNSCC) following the results of the KEYNOTE-048 trial, which demonstrated a longer overall survival (OS) in comparison to the EXTREME chemotherapy regimen in patients with a combined positive score (CPS) ≥1. In this article, we provide retrospective real-world data on the role of pembrolizumab monotherapy as first-line systemic therapy for HNSCC across 18 centers in the UK from March 20, 2020 to May 31, 2021. 211 patients were included, and in the efficacy analysis, the objective response rate (ORR) was 24.7%, the median progression-free survival (PFS) was 4.8 months (95% confidence interval [CI]: 3.6-6.1), and the median OS was 10.8 months (95% CI 9.0-12.5). Pembrolizumab monotherapy was well tolerated, with 18 patients having to stop treatment owing to immune-related adverse events (irAEs). 53 patients proceeded to second-line treatment with a median PFS2 of 10.2 months (95% CI: 8.8-11.5). Moreover, patients with documented irAEs had a statistically significant longer median PFS (11.3 vs. 3.3 months; log-rank p value = <.001) and median OS (18.8 vs. 8.9 months; log-rank p value <.001). The efficacy and safety of pembrolizumab first-line monotherapy for HNSCC has been validated using real-world data.

High numbers of COVID-19 patients transit through non-COVID wards, and associated healthcare workers have high infection rates: An observational cross-sectional study.

Infection risk is high in healthcare workers working with COVID-19 patients but the risk in non-COVID clinical environments is less clear. We measured infection rates early in the pandemic by SARS-CoV-2 antibody and/or a positive PCR test in 1118 HCWs within various hospital environments with particular focus on non-COVID clinical areas. Infection risk on non-COVID wards was estimated through the surrogate metric of numbers of patients transferred from a non-COVID to a COVID ward. Staff infection rates increased with likelihood of COVID exposure and suggested high risk in non-COVID clinical areas (non patient-facing 23.2% versus patient-facing in either non-COVID environments 31.5% or COVID wards 44%). High numbers of patients admitted to COVID wards had initially been admitted to designated non-COVID wards (22-48% at peak). Infection risk was high during a pandemic in all clinical environments and non-COVID designation may provide false reassurance. Our findings support the need for common personal protective equipment standards in all clinical areas, irrespective of COVID/non-COVID designation.

Coexistent antiphospholipid syndrome and myeloproliferative neoplasm.

Antiphospholipid syndrome (APS) and myeloproliferative neoplasms (MPN) are associated with an increased risk of thrombosis. The optimal management of patients with coexistent APS and MPN has not been defined. A single centre and systematic literature review of patients with coexistent APS and MPN was performed. Cases were divided into two groups based on whether they met international consensus criteria for APS. Of the 12 studies identified, eight were excluded (leaving five of a total 54 patients), as although antiphospholipid antibodies (aPL) were documented, the diagnosis of APS was not conclusively demonstrated. Another ten patients with definite APS were identified at our centre. Fifteen patients (ten females, five males) were therefore included in this analysis (eleven definite APS and four highly likely), median age 44 (range: 13-71) years. Nine had polycythaemia vera and six, essential thrombocythaemia. Thirteen of the 15 patients (86.7%) had thrombotic APS (seven with initial venous events and six arterial) and two (13.3%) had obstetric APS. Nine patients were single-positive, and six double-positive for aPL. None were triple aPL-positive. Four patients at our centre had recurrent thrombotic/obstetric events, including while on anticoagulation/antiplatelet treatment.

Correlation between tobacco control policies and mortality of haematological cancers across Europe: An ecological study.

INTRODUCTION: To determine the correlation between tobacco control policies and mortality of haematological malignancies: leukemia, lymphoma and multiple myeloma (MM). METHODS: Ecological study with the countries as the unit of analysis. Tobacco Control Scale (TCS) scores from 2010, 2013 and 2016 were used as measures for the level of tobacco control policy implementation in 27 European countries. Mortality rates for leukemia, lymphoma, and MM, were obtained from the WHO Mortality Database and the European Cancer Information System for each country for 2010, 2013, 2015 and 2018. Correlation between yearly TCS scores and mortality rates from the same and prospective years were calculated using Spearman's rank correlation coefficients (rsp) and 95% confidence intervals (95% CI) (2010 TCS scores vs 2010, 2013, 2015, 2018 mortality rates; 2013 TCS scores vs 2013, 2015, 2018 mortality rates; and 2016 TCS scores vs 2018 mortality rates). RESULTS: The 2010 TCS scores were significantly negatively associated with leukemia mortality rates in 2013 (rsp=-0.58; 95% CI: -0.79, -0.24; p=0.002), 2015 (rsp=-0.65; 95% CI: -0.85, -0.30; p=0.001) and 2018 (rsp=-0.44; 95% CI: -0.71, -0.06; p=0.021). TCS scores from 2013 and 2016 had significant negative associations with leukemia mortality in all prospective years. TCS scores did not demonstrate consistent correlations with lymphoma and MM mortality. CONCLUSIONS: The level of tobacco control policies in European countries correlates negatively with leukemia mortality at ecological level, with no correlation seen for lymphoma and MM. This study advocates that increased tobacco control implementation may improve leukemia mortality.

Anti-protein C antibodies and acquired protein C resistance in SLE: novel markers for thromboembolic events and disease activity?

OBJECTIVES: Risk factors for thromboembolism in SLE are poorly understood. We hypothesized a possible role for protein C, based on its dual activity in inflammation and haemostasis and on the evidence of an association between acquired activated protein C (APC) resistance (APCR) and high-avidity anti-protein C antibodies (anti-PC) with a severe thrombotic phenotype in venous thrombosis APS patients. METHODS: In a cross-sectional study of 156 SLE patients, the presence and avidity of IgG anti-PC was established by in house-ELISA, and APCR to exogenous recombinant human APC (rhAPC) and Protac (which activates endogenous protein C) was assessed by thrombin generation-based assays. Associations with aPL profile, thrombotic history and disease activity (BILAG and SLEDAI-2K) were also established. RESULTS: Anti-PC were detected in 54.5% of patients and APCR in 59%. Anti-PC positivity was associated with APCR to both rhAPC (P <0.0001) and Protac (P =0.0001). High-avidity anti-PC, detected in 26.3% of SLE patients, were associated with APCR in patients with thrombosis only (P <0.05), and with the development of thrombosis over time (range: 0-52 years; P =0.014). High-avidity anti-PC levels correlated with SLEDAI-2K (P =0.033) and total BILAG (P =0.019); SLEDAI-2K correlated inversely with APCR to Protac (P =0.004). CONCLUSION: Anti-PC occur in patients with SLE, independently of aPL profile, and are associated with APCR. High-avidity anti-PC are associated with thrombosis and with active disease and might prove a novel marker to monitor the risk of thrombosis and disease progression in SLE.

Systemic mastocytosis: variable manifestations can lead to a challenging diagnostic process.

Systemic mastocytosis results from proliferation and activation of an abnormal mast cell clone. It is a heterogeneous disorder with clinical manifestations ranging from skin lesions alone to aggressive multi-organ infiltration and decreased survival. Given these varied manifestations, diagnosis can be difficult. We describe the case of a woman who presented with rash and diarrhoea and had a history of anaphylactic reactions. Over a protracted period, the patient's symptoms were investigated by a number of specialties including gastroenterology, dermatology, immunology and haematology. Morphological, immunohistochemical and molecular analysis of bone marrow samples ultimately led to a diagnosis of systemic mastocytosis. Management with leukotriene and histamine antagonists resulted in significant improvement in symptoms and quality of life. The case serves to highlight the protean manifestations of systemic mastocytosis, the tests available to diagnose it and the agents available to treat it.