IBRUTINIB AND RITUXIMAB AS FIRST LINE THERAPY FOR MANTLE CELL LYMPHOMA: A MULTICENTRE, REAL-WORLD UK STUDY

Background: Ibrutinib (IBR) is an oral covalent Bruton tyrosine kinase inhibitor (BTKi), licensed for treatment of relapsed or refractory mantle cell lymphoma (MCL). Under NHS interim Covid-19 agreements in England, IBR with or without rituximab (R) was approved for the frontline treatment for MCL patients (pts) as a safer alternative to conventional immunochemotherapy. Although recent phase 2 studies have reported high response rates in low-risk patients for this combination in the frontline setting, randomised phase 3 and real-world data are currently lacking. Aims: To describe the real-world response rates (overall response rate (ORR), complete response (CR) rate) and toxicity profile of IBR +/-R in adult patients with previously untreated MCL. Methods: Following institutional approval, adults commencing IBR +/-R for untreated MCL under interim Covid-19 arrangements were prospectively identified by contributing centres. Hospital records were interrogated for demographic, pathology, response, toxicity and survival data. ORR/CR were assessed per local investigator according to the Lugano criteria using CT and/or PET-CT. Results: Data were available for 66 pts (72.7% male, median age 71 years, range 41-89). Baseline demographic and clinical features are summarised in Table 1. 23/66 pts (34.8%) had high-risk disease (defined as presence of TP53 mutation/deletion, blastoid or pleomorphic variant MCL, or Ki67%/MiB-1 ≥30%). IBR starting dose was 560mg in 56/62 pts (90%) and was given with R in 22/64 pts (34%). At a median follow up of 8.7 months (m) (range 0-18.6), pts had received a median of 7 cycles of IBR. 19/60 pts (32%) required a dose reduction or delay in IBR treatment. New atrial fibrillation and grade ≥3 any-cause toxicity occurred in 3/59 pts (5.8%) and 8/57 (14.0%) respectively. For the whole population and high-risk pts only, ORR was 74.4% and 64.7% respectively (p=0.2379), with a median time to response of 3.8m, coinciding with the first response assessment scan. Seven pts (16.7%), of whom 2 had highrisk disease, attained CR at a median of 6.0m. ORR for pts receiving vs not receiving R were 84.2% and 66.7% respectively (p=0.1904). IBR was discontinued in 20/61 pts (32.8%) at a median time to discontinuation of 4.1m, due to progressive disease (PD, 19.7%), toxicity (4.9%), death (3.3%;1 pt each of Covid-19 and E. coli infection), pt choice (3.3%) and other unspecified reasons (1.6%). 15/66 pts (22.7%) overall and 7/23 (30.4%) with high-risk disease progressed on IBR at a median time to PD of 4.0m. No pts underwent autologous stem cell transplantation consolidation during the study period. 12/57 pts (21.1%) received second line treatment (R-chemotherapy n=7, Nordic MCL protocol n=2, VR-CAP n=2, pirtobrutinib n=1). Response to second line treatment was CR in 4/11 pts, PD in 7/11. Of the 2 Nordic-treated patients, 1 had CR after cycle 2 and 1 PD. Fourteen pts (21.2%) died during the follow up period, due to MCL (n=11), Covid-19 (n=2) and congestive cardiac failure (n=1). Overall survival was lower for patients with high-risk disease (HR 0.55, p=0.038). Image: Summary/Conclusion: In this real-world UK cohort of pts receiving first-line IBR +/-R for MCL, including older and high-risk pts, we report high ORR rates in a similar range to the phase II Geltamo IMCL-2015 study of combination IBR-R in an exclusively low-risk population. Documented CR rates were lower, possibly reflecting a low usage of rituximab in the Covid-19 pandemic as well as CT assessment of response. Treatment was generally well tolerated, with low rates of toxicityrelated treatment discontinuation. The study is ongoing.

COVID-19 survey burden for health care workers: literature review and audit.

OBJECTIVES: Concerns have been raised about the quantity and quality of research conducted during the COVID-19 pandemic, particularly related to the mental health and wellbeing of health care workers (HCWs). For understanding the volume, source, methodological rigour and degree of overlap in COVID-19, studies were conducted among HCWs in the United Kingdom (UK). STUDY DESIGN: Mixed methods approach, literature review and audit. METHODS: First, a literature review of published research studies and second, an audit of studies HCWs have been invited to complete. For the literature review, we searched Medline, PsycINFO and Nexis, webpages of three medical organisations (Royal Society of Medicine, Royal College of Nursing and British Medical Association), and the YouGov website. For the audit, a non-random purposive sample of six HCWs from different London NHS Trusts reviewed email, WhatsApp and SMS messages they received for study invitations. RESULTS: The literature review identified 27 studies; the audit identified 70 study invitations. Studies identified by the literature review were largely of poor methodological rigour: only eight studies (30%) provided response rate, one study (4%) reported having ethical approval, and one study (4%) reported funding details. There was substantial overlap in the topics measured. In the audit, volunteers received a median of 12 invitations. The largest number of study invitations were for national surveys (n = 23), followed by local surveys (n = 16) and research surveys (n = 8). CONCLUSION: HCWs have been asked to complete numerous surveys that frequently have methodological shortcomings and overlapping aims. Many studies do not follow scientific good-practice and generate questionable, non-generalisable results.

Abnormal haematological parameters in COVID 19 positive patents. A single centre study from the United Kingdom

Content: The current COVID - 19 global pandemic, caused by the novel coronavirus, SARS-CoV-2, is going through a second wave in many countries and has resulted in an unprecedented mortality and morbidity. The typical clinical presentation includes flu-like symptoms, such as fever, cough and asthenia, and also COVID-19 specific anosmia;however, the symptom spectrum spreads from being asymptomatic, to a severe acute respiratory distress syndrome, to multiple organ failure. Aim: The aim of this study is to evaluate the abnormalities seen in the full blood count parameters of patients with positive qPCR test for SARS-CoV-2 infections. Method: This was a retrospective analysis of all full blood count parameters from patients who tested positive for SARS-CoV-2 following a qPCR test, and were admitted to hospital with symptoms in the first wave of COVID-19, from March 2020 to June 2020. 12 different parameters were assessed for any abnormalities, including: haemoglobin (Hb), white blood cell count (WCC), neutrophil, lymphocytes, eosinophils, basophils, platelets, Mean Cell Volume (MCV), Mean Cell Haemoglobin (MCH), haematocrit (HCT), and red blood cell distribution width (RDW). Inclusion criteria for the study were: admission to hospital, positive qPCR test, no known malignancy or HIV, and no current immunosuppressive or chemo- therapy. The full blood count parameters from all patients admitted with suspected SARS-CoV-2 infection were extracted from the analyser. Only the patients with positive qPCR test were selected for the study. Results: Samples from a total of 278 patients (162 male and 116 female) were analysed. The median age of patients was 76 (range from 1 year to 99 years). Abnormal WBC count with a predominant leucocytosis was seen in 27% of patients. 1.4% patients had abnormal RBC, while 41% had abnormal Hb, with 18% of patients with Hb <100 gm/l. HCT was abnormal in 60% of patients. Furthermore, abnormal neutrophil and lymphocyte counts were detected in 43% and 54% patients respectively. Lymphopenia and thrombocytopenia were seen in 52% and 13% of patients respectively. No evidence of reduced total white cell count was seen. Abnormal monocytes were seen in 15% of patients. There was no striking eosinophilia, but rather a decrease in circulating eosinophils in 82% of patients. Overall, the changes were more pronounced in HCT, lymphocyte and eosinophil counts. Conclusion: Significant abnormalities in full blood count parameters seen in COVID-19 patients could possibly help to elucidate the pathogenesis of SARS-CoV-2 infection along with other biomedical parameters. These abnormal parameters can be modelled to a risk stratifying algorithm to predict the severity of the COVID-19 infection in a hospital setting.

Parental perceptions of COVID-19-like illness in their children.

OBJECTIVES: The objective of the study is to explore parents' perceptions of COVID-19-like symptoms in their child and attitudes towards isolating from others in the household when unwell. STUDY DESIGN: The study used qualitative, semistructured interviews. METHODS: The study involved thirty semistructured telephone interviews with parents of children between 4 and 18 years. Thirty semistructured telephone interviews with parents of children between 4 and 18 years. RESULTS: We found four themes relating to symptom attribution ('normalising symptoms', 'err on the side of caution', 'experience of temperature', 'symptoms not normal for us'). In general, parents were more likely to attribute symptoms to COVID-19 if a temperature was present or the symptoms were perceived as 'unusual' for their family. Four themes relating to self-isolation ('difficult to prevent contact with children', 'isolation would be no different to lockdown life', 'ability to get food and supplies', 'limited space'). Parents believed they would find isolation within the household difficult or impossible if they had dependent children, had limited space or could not shop for groceries. CONCLUSIONS: The findings highlight complexities in symptom perception, attribution and household isolation. We suggest that they can be overcome by (a) providing better guidance on what symptoms require action, (b) providing guidance as to how to prevent infection within the household and (c) by supporting families with grocery shopping through a potential second or third wave.