The physical exam's role in determining dose-limiting toxicity prior to immunochemotherapy administration in lymphoma.

INTRODUCTION: The COVID-19 pandemic has introduced new challenges to healthcare access and delivery. It is critical to identify areas for innovation within oncologic clinical practice to maintain high quality care. We evaluated the potential utility of telemedicine initiatives for patients with lymphoma undergoing immunochemotherapy. We conducted a retrospective review of adult lymphoma patients receiving R-CHOP + /- R, R-ICE, R-GEMOX, and R-DHAP at our institution in the last three years (2017-2019) and identified cycles for which dose modifications were required. METHODS: We reviewed 1290 total treatment cycles in 301 unique patients, 1102 cycles (85.4%) were R-CHOP + /- R, 105 (8.1%) were R-ICE, 71 (5.5%) were R-GEMOX, and 12 (0.9%) were R-DHAP. We identified that 144 cycles (11.2%) were subject to dosing adjustments. We retrospectively reviewed laboratory results, patient history, and/or physical exam findings that informed dose modifications. RESULTS: Of the 144 dose adjustments, 11% of cycles contained dose increases due to a well-tolerated previous dose noted in the clinical assessment. The remaining 128 modified cycles were dose reductions. Notably, only 7/128 dose reductions were based on physical exam findings alone, due solely to a change in patient body weight. As patients are routinely weighed immediately prior to chemotherapy administration, effectively no dose modifications (0/144) were exclusively based on abnormal physical exam finding during a pre-infusion assessment. CONCLUSION: These findings suggest that pre-infusion assessments may be amenable to virtual visits for lymphoma patients undergoing immunochemotherapy.

A digital ecosystem as an institutional field: curated peer production as a response to institutional voids revealed by COVID ‐19

This paper investigates the ecosystem dynamics of the Open-source [COVID-19] Medical Supplies network that arose to fill the institutional void revealed by state and private sector failures to stockpile and supply enough personal protective equipment. Theoretically, the paper adds correctives to extant institutional theory accounts of entrepreneurship filling institutional voids, showing that these can be filled rapidly and normatively by digital entrepreneurial ecosystems allied with peer production networks. These were able to transform the boundary conditions of a routinized system, refixing its autopoiesis innovatively. The COVID-19 epidemic galvanized hundreds of thousands of volunteer "makers" around the world to cooperate to meet urgent demand for medical supplies. A digital entrepreneurial ecosystem arose in response to the problem of critical equipment shortages, connecting global, expert-curated know-how with local production equipment. We contribute to the theory of institutional voids by documenting and analyzing how the formation and emergent processes that created and sustained a Digital Peer Production Ecosystem based on self-organization, expert curation and scalability, successfully catalyzed local initiatives worldwide. Institutional voids are not just barriers to entrepreneurship;they are also opportunities.

The Feasibility of Virtual Toxicity Assessments in Lymphoma Patients Receiving Immunochemotherapy

Background: In recent years, there has been a growing interest in telemedicine initiatives that maximize outcomes, reduce healthcare costs, and improve quality. The COVID-19 pandemic reduced healthcare access for many patients, including those undergoing chemotherapy, and thus accelerated these initiatives. We sought to evaluate the potential utility of telemedicine initiatives for lymphoma patients undergoing immunochemotherapy. Methods: To address this question, we conducted a retrospective review of adult lymphoma patients receiving R-CHOP +/- R, R-ICE, R-GEMOX, and R-DHAP at our institution in the last three years (2017-2019), and identified those for which dose modifications were required. Dose modifications were defined as a change in prescribed dose from the preceding cycle, or a change in the administered dose by 10% or greater. Laboratory results, patient history, and/or physical exam findings that informed dose modifications were retrospectively identified. Results: Of the 1,290 total treatment cycles identified in 301 unique patients, 1,102 cycles (85.4%) were R-CHOP +/- R, 105 (8.1%) were R-ICE, 71 (5.5%) were R-GEMOX, and 12 (0.9%) were R-DHAP. We found that 144 cycles (11.2%) were subject to dosing adjustments. The cohort of patients that received dose adjustments was comprised of 104 unique patients, of which 87 (60.4%) were male and 57 (39.6%) were female. Average age at diagnosis was 64 years old (Range: 22-91). Our cohort represented greater than 10 different lymphoma subtypes, most commonly Diffuse Large B-cell lymphoma (66.3%), Follicular lymphoma (14.5%), and Peripheral T-cell lymphomas (7.7%). We examined the basis for each dose adjustment by reviewing the clinical records from visits immediately preceding the dose adjusted cycle. Of the 144 dose adjustments, 11% of cycles contained dose increases due to a well-tolerated previous dose noted in the clinical assessment based on a combination of laboratory findings, interim history, and physical exam. The remaining 89% of adjustments (n=128) were dose reductions. The decision to dose reduce was most commonly informed by the clinical history (n=104, 81%). The clinical history was dichotomized into newly reported patient symptoms (69/104) or interim complications (35/104), usually infectious (n=26). Clinical assessments utilized laboratory findings as a rationale for dose reductions in 33/128 (26%) of cycles, most of which were secondary to myelosuppression (28/33 cycles). In contrast, only 7/128 dose reductions were based on physical exam findings alone, all of which were due to a change in patient body weight. As patients are routinely weighed immediately prior to chemotherapy administration, effectively no dose modifications (0/144) were exclusively based on abnormal physical exam finding during a pre-infusion assessment. Conclusions: The inability to perform a complete physical exam is a notable limitation of telemedicine initiatives. However, in an unselected group of lymphoma patients treated with immunochemotherapy, who subsequently had dose reductions to their regimens, we have found that all of the dose modifications were based on laboratory findings or the patient history, both of which are amenable to virtual visits. In stark contrast, no dose modifications were prompted by an abnormal physical exam finding alone. While further studies are needed, the data reviewed supports the implementation of telemedicine initiatives in lymphoma patients undergoing immunochemotherapy during the pandemic and potentially long term. Disclosures Phillips:Karyopharm: Consultancy;AstraZeneca: Consultancy;Beigene: Consultancy;Abbvie: Consultancy, Research Funding;Pharmacyclics: Consultancy;Bayer: Consultancy, Research Funding;BMS: Consultancy;Incyte: Consultancy, Other: travel expenses;Seattle Genetics: Consultancy;Cardinal Health: Consultancy.

The impact of an immuno-oncology service at a regional cancer centre based in the north west of the UK.

This article discusses the implementation and development of a centralised immuno-oncology service. As the indications and licensing of oncological immune checkpoint inhibitors (ICIs) expanded rapidly, they brought with them increasing challenges. The article evaluates the impact of an immuno-oncology service, focusing on the following areas: admission rates due to immune-related adverse events (irAEs), number of bed days occupied due to immunotherapy toxicity and the incidence of Grade 3 and 4 (severe and life-threatening) irAEs. The article will also give an overview of patients requiring acute and subsequent management of toxicity as a percentage of the overall patients commenced on immunotherapy. The ultimate aim of the article is to highlight the importance of toxicity management and the overall benefits of a immuno-oncology service. The article will also discuss the impact of COVID-19 on the immuno-oncology service, highlighting the ways in which the team has adapted to the current environment to ensure high standards of patient care have been maintained.

Mortality Among Adults With Cancer Undergoing Chemotherapy or Immunotherapy and Infected With COVID-19.

Importance: Large cohorts of patients with active cancers and COVID-19 infection are needed to provide evidence of the association of recent cancer treatment and cancer type with COVID-19 mortality. Objective: To evaluate whether systemic anticancer treatments (SACTs), tumor subtypes, patient demographic characteristics (age and sex), and comorbidities are associated with COVID-19 mortality. Design, Setting, and Participants: The UK Coronavirus Cancer Monitoring Project (UKCCMP) is a prospective cohort study conducted at 69 UK cancer hospitals among adult patients (≥18 years) with an active cancer and a clinical diagnosis of COVID-19. Patients registered from March 18 to August 1, 2020, were included in this analysis. Exposures: SACT, tumor subtype, patient demographic characteristics (eg, age, sex, body mass index, race and ethnicity, smoking history), and comorbidities were investigated. Main Outcomes and Measures: The primary end point was all-cause mortality within the primary hospitalization. Results: Overall, 2515 of 2786 patients registered during the study period were included; 1464 (58%) were men; and the median (IQR) age was 72 (62-80) years. The mortality rate was 38% (966 patients). The data suggest an association between higher mortality in patients with hematological malignant neoplasms irrespective of recent SACT, particularly in those with acute leukemias or myelodysplastic syndrome (OR, 2.16; 95% CI, 1.30-3.60) and myeloma or plasmacytoma (OR, 1.53; 95% CI, 1.04-2.26). Lung cancer was also significantly associated with higher COVID-19-related mortality (OR, 1.58; 95% CI, 1.11-2.25). No association between higher mortality and receiving chemotherapy in the 4 weeks before COVID-19 diagnosis was observed after correcting for the crucial confounders of age, sex, and comorbidities. An association between lower mortality and receiving immunotherapy in the 4 weeks before COVID-19 diagnosis was observed (immunotherapy vs no cancer therapy: OR, 0.52; 95% CI, 0.31-0.86). Conclusions and Relevance: The findings of this study of patients with active cancer suggest that recent SACT is not associated with inferior outcomes from COVID-19 infection. This has relevance for the care of patients with cancer requiring treatment, particularly in countries experiencing an increase in COVID-19 case numbers. Important differences in outcomes among patients with hematological and lung cancers were observed.

Association between vitamin D supplementation or serum vitamin D level and susceptibility to SARS-CoV-2 infection or COVID-19 including clinical course, morbidity and mortality outcomes? A systematic review.

OBJECTIVE: To systemically review and critically appraise published studies of the association between vitamin D supplementation or serum vitamin D level and susceptibility to SARS-CoV-2 infection or COVID-19, including clinical course, morbidity and mortality outcomes. DESIGN: Systematic review. DATA SOURCES: MEDLINE (OVID), Embase (OVID), Cochrane Central Register of Controlled Trials, MedRxiv and BioRxiv preprint databases. COVID-19 databases of the WHO, Cochrane, CEBM Oxford and Bern University up to 10 June 2020. STUDY SELECTION: Studies that assessed vitamin D supplementation and/or low serum vitamin D in patients acutely ill with, or at risk of, severe betacoronavirus infection (SARS-CoV, MERS-CoV, SARS-CoV-2). DATA EXTRACTION: Two authors independently extracted data using a predefined data extraction form and assessed risk of bias using the Downs and Black Quality Assessment Checklist. RESULTS: Searches elicited 449 papers, 59 studies were eligible full-text assessment and 4 met the eligibility criteria of this review. The four studies were narratively synthesised and included (1) a cross-sectional study (n=107) suggesting an inverse association between serum vitamin D and SARS-CoV-2; (2) a retrospective cohort study (348 598 participants, 449 cases) in which univariable analysis showed that vitamin D protects against COVID-19; (3) an ecological country level study demonstrating a negative correlation between vitamin D and COVID-19 case numbers and mortality; and (4) a case-control survey (n=1486) showing cases with confirmed/probable COVID-19 reported lower vitamin D supplementation. All studies were at high/unclear risk of bias. CONCLUSION: There is no robust evidence of a negative association between vitamin D and COVID-19. No relevant randomised controlled trials were identified and there is no robust peer-reviewed published evidence of association between vitamin D levels and severity of symptoms or mortality due to COVID-19. Guideline producers should acknowledge that benefits of vitamin D supplementation in COVID-19 are as yet unproven despite increasing interest.

Considerations for Use of Hematopoietic Growth Factors in Patients With Cancer Related to the COVID-19 Pandemic.

Hematopoietic growth factors, including erythrocyte stimulating agents (ESAs), granulocyte colony-stimulating factors, and thrombopoietin mimetics, can mitigate anemia, neutropenia, and thrombocytopenia resulting from chemotherapy for the treatment of cancer. In the context of pandemic SARS-CoV-2 infection, patients with cancer have been identified as a group at high risk of morbidity and mortality from this infection. Our subcommittee of the NCCN Hematopoietic Growth Factors Panel convened a voluntary group to review the potential value of expanded use of such growth factors in the current high-risk environment. Although recommendations are available on the NCCN website in the COVID-19 Resources Section (https://www.nccn.org/covid-19/), these suggestions are provided without substantial context or reference. Herein we review the rationale and data underlying the suggested alterations to the use of hematopoietic growth factors for patients with cancer in the COVID-19 era.

COVID-19 prevalence and mortality in patients with cancer and the effect of primary tumour subtype and patient demographics: a prospective cohort study.

BACKGROUND: Patients with cancer are purported to have poor COVID-19 outcomes. However, cancer is a heterogeneous group of diseases, encompassing a spectrum of tumour subtypes. The aim of this study was to investigate COVID-19 risk according to tumour subtype and patient demographics in patients with cancer in the UK. METHODS: We compared adult patients with cancer enrolled in the UK Coronavirus Cancer Monitoring Project (UKCCMP) cohort between March 18 and May 8, 2020, with a parallel non-COVID-19 UK cancer control population from the UK Office for National Statistics (2017 data). The primary outcome of the study was the effect of primary tumour subtype, age, and sex and on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevalence and the case-fatality rate during hospital admission. We analysed the effect of tumour subtype and patient demographics (age and sex) on prevalence and mortality from COVID-19 using univariable and multivariable models. FINDINGS: 319 (30·6%) of 1044 patients in the UKCCMP cohort died, 295 (92·5%) of whom had a cause of death recorded as due to COVID-19. The all-cause case-fatality rate in patients with cancer after SARS-CoV-2 infection was significantly associated with increasing age, rising from 0·10 in patients aged 40-49 years to 0·48 in those aged 80 years and older. Patients with haematological malignancies (leukaemia, lymphoma, and myeloma) had a more severe COVID-19 trajectory compared with patients with solid organ tumours (odds ratio [OR] 1·57, 95% CI 1·15-2·15; p<0·0043). Compared with the rest of the UKCCMP cohort, patients with leukaemia showed a significantly increased case-fatality rate (2·25, 1·13-4·57; p=0·023). After correction for age and sex, patients with haematological malignancies who had recent chemotherapy had an increased risk of death during COVID-19-associated hospital admission (OR 2·09, 95% CI 1·09-4·08; p=0·028). INTERPRETATION: Patients with cancer with different tumour types have differing susceptibility to SARS-CoV-2 infection and COVID-19 phenotypes. We generated individualised risk tables for patients with cancer, considering age, sex, and tumour subtype. Our results could be useful to assist physicians in informed risk-benefit discussions to explain COVID-19 risk and enable an evidenced-based approach to national social isolation policies. FUNDING: University of Birmingham and University of Oxford.

Immune checkpoint blockade: releasing the breaks or a protective barrier to COVID-19 severe acute respiratory syndrome?

The rapid emergence of COVID-19 has sent shockwaves through healthcare systems globally, with cancer patients at increased risk. The interplay of the virus and host immune system has been implicated in the development of ARDS. Immunotherapy agents have the potential to adversely potentiate this phenomenon, requiring careful real-world observation.

COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study.

BACKGROUND: Individuals with cancer, particularly those who are receiving systemic anticancer treatments, have been postulated to be at increased risk of mortality from COVID-19. This conjecture has considerable effect on the treatment of patients with cancer and data from large, multicentre studies to support this assumption are scarce because of the contingencies of the pandemic. We aimed to describe the clinical and demographic characteristics and COVID-19 outcomes in patients with cancer. METHODS: In this prospective observational study, all patients with active cancer and presenting to our network of cancer centres were eligible for enrolment into the UK Coronavirus Cancer Monitoring Project (UKCCMP). The UKCCMP is the first COVID-19 clinical registry that enables near real-time reports to frontline doctors about the effects of COVID-19 on patients with cancer. Eligible patients tested positive for severe acute respiratory syndrome coronavirus 2 on RT-PCR assay from a nose or throat swab. We excluded patients with a radiological or clinical diagnosis of COVID-19, without a positive RT-PCR test. The primary endpoint was all-cause mortality, or discharge from hospital, as assessed by the reporting sites during the patient hospital admission. FINDINGS: From March 18, to April 26, 2020, we analysed 800 patients with a diagnosis of cancer and symptomatic COVID-19. 412 (52%) patients had a mild COVID-19 disease course. 226 (28%) patients died and risk of death was significantly associated with advancing patient age (odds ratio 9·42 [95% CI 6·56-10·02]; p<0·0001), being male (1·67 [1·19-2·34]; p=0·003), and the presence of other comorbidities such as hypertension (1·95 [1·36-2·80]; p<0·001) and cardiovascular disease (2·32 [1·47-3·64]). 281 (35%) patients had received cytotoxic chemotherapy within 4 weeks before testing positive for COVID-19. After adjusting for age, gender, and comorbidities, chemotherapy in the past 4 weeks had no significant effect on mortality from COVID-19 disease, when compared with patients with cancer who had not received recent chemotherapy (1·18 [0·81-1·72]; p=0·380). We found no significant effect on mortality for patients with immunotherapy, hormonal therapy, targeted therapy, radiotherapy use within the past 4 weeks. INTERPRETATION: Mortality from COVID-19 in cancer patients appears to be principally driven by age, gender, and comorbidities. We are not able to identify evidence that cancer patients on cytotoxic chemotherapy or other anticancer treatment are at an increased risk of mortality from COVID-19 disease compared with those not on active treatment. FUNDING: University of Birmingham, University of Oxford.