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      Management of patients with multiple myeloma in the era of COVID-19 pandemic: a consensus paper from the European Myeloma Network (EMN)

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          Abstract

          Patients with multiple myeloma (MM) seem to be at increased risk for more severe COVID-19 infection and associated complications due to their immunocompromised state, the older age and comorbidities. The European Myeloma Network has provided an expert consensus statement in order to guide therapeutic decisions in the era of the COVID-19 pandemic. Patient education for personal hygiene and social distancing measures, along with treatment individualization, telemedicine and continuous surveillance for early diagnosis of COVID-19 are essential. In countries or local communities where COVID-19 infection is widely spread, MM patients should have a PCR test of nasopharyngeal swab for SARS-CoV-2 before hospital admission, starting a new treatment line, cell apheresis or ASCT in order to avoid ward or community spread and infections. Oral agent-based regimens should be considered, especially for the elderly and frail patients with standard risk disease, whereas de-intensified regimens for dexamethasone, bortezomib, carfilzomib and daratumumab should be used based on patient risk and response. Treatment initiation should not be postponed for patients with end organ damage, myeloma emergencies and aggressive relapses. Autologous (and especially allogeneic) transplantation should be delayed and extended induction should be administered, especially in standard risk patients and those with adequate MM response to induction. Watchful waiting should be considered for standard risk relapsed patients with low tumor burden, and slow biochemical relapses. The conduction of clinical trials should continue with appropriate adaptations to the current circumstances. Patients with MM and symptomatic COVID-19 disease should interrupt anti-myeloma treatment until recovery. For patients with positive PCR test for SARS-CoV-2, but with no symptoms for COVID-19, a 14-day quarantine should be considered if myeloma-related events allow the delay of treatment. The need for surveillance for drug interactions due to polypharmacy is highlighted. The participation in international COVID-19 cancer registries is greatly encouraged.

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          Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy

          In December 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) emerged in China and has spread globally, creating a pandemic. Information about the clinical characteristics of infected patients who require intensive care is limited.
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            Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China

            China and the rest of the world are experiencing an outbreak of a novel betacoronavirus known as severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). 1 By Feb 12, 2020, the rapid spread of the virus had caused 42 747 cases and 1017 deaths in China and cases have been reported in 25 countries, including the USA, Japan, and Spain. WHO has declared 2019 novel coronavirus disease (COVID-19), caused by SARS-CoV-2, a public health emergency of international concern. In contrast to severe acute respiratory system coronavirus and Middle East respiratory syndrome coronavirus, more deaths from COVID-19 have been caused by multiple organ dysfunction syndrome rather than respiratory failure, 2 which might be attributable to the widespread distribution of angiotensin converting enzyme 2—the functional receptor for SARS-CoV-2—in multiple organs.3, 4 Patients with cancer are more susceptible to infection than individuals without cancer because of their systemic immunosuppressive state caused by the malignancy and anticancer treatments, such as chemotherapy or surgery.5, 6, 7, 8 Therefore, these patients might be at increased risk of COVID-19 and have a poorer prognosis. On behalf of the National Clinical Research Center for Respiratory Disease, we worked together with the National Health Commission of the People's Republic of China to establish a prospective cohort to monitor COVID-19 cases throughout China. As of the data cutoff on Jan 31, 2020, we have collected and analysed 2007 cases from 575 hospitals (appendix pp 4–9 for a full list) in 31 provincial administrative regions. All cases were diagnosed with laboratory-confirmed COVID-19 acute respiratory disease and were admitted to hospital. We excluded 417 cases because of insufficient records of previous disease history. 18 (1%; 95% CI 0·61–1·65) of 1590 COVID-19 cases had a history of cancer, which seems to be higher than the incidence of cancer in the overall Chinese population (285·83 [0·29%] per 100 000 people, according to 2015 cancer epidemiology statistics 9 ). Detailed information about the 18 patients with cancer with COVID-19 is summarised in the appendix (p 1). Lung cancer was the most frequent type (five [28%] of 18 patients). Four (25%) of 16 patients (two of the 18 patients had unknown treatment status) with cancer with COVID-19 had received chemotherapy or surgery within the past month, and the other 12 (25%) patients were cancer survivors in routine follow-up after primary resection. Compared with patients without cancer, patients with cancer were older (mean age 63·1 years [SD 12·1] vs 48·7 years [16·2]), more likely to have a history of smoking (four [22%] of 18 patients vs 107 [7%] of 1572 patients), had more polypnea (eight [47%] of 17 patients vs 323 [23%] of 1377 patients; some data were missing on polypnea), and more severe baseline CT manifestation (17 [94%] of 18 patients vs 1113 [71%] of 1572 patients), but had no significant differences in sex, other baseline symptoms, other comorbidities, or baseline severity of x-ray (appendix p 2). Most importantly, patients with cancer were observed to have a higher risk of severe events (a composite endpoint defined as the percentage of patients being admitted to the intensive care unit requiring invasive ventilation, or death) compared with patients without cancer (seven [39%] of 18 patients vs 124 [8%] of 1572 patients; Fisher's exact p=0·0003). We observed similar results when the severe events were defined both by the above objective events and physician evaluation (nine [50%] of 18 patients vs 245 [16%] of 1572 patients; Fisher's exact p=0·0008). Moreover, patients who underwent chemotherapy or surgery in the past month had a numerically higher risk (three [75%] of four patients) of clinically severe events than did those not receiving chemotherapy or surgery (six [43%] of 14 patients; figure ). These odds were further confirmed by logistic regression (odds ratio [OR] 5·34, 95% CI 1·80–16·18; p=0·0026) after adjusting for other risk factors, including age, smoking history, and other comorbidities. Cancer history represented the highest risk for severe events (appendix p 3). Among patients with cancer, older age was the only risk factor for severe events (OR 1·43, 95% CI 0·97–2·12; p=0·072). Patients with lung cancer did not have a higher probability of severe events compared with patients with other cancer types (one [20%] of five patients with lung cancer vs eight [62%] of 13 patients with other types of cancer; p=0·294). Additionally, we used a Cox regression model to evaluate the time-dependent hazards of developing severe events, and found that patients with cancer deteriorated more rapidly than those without cancer (median time to severe events 13 days [IQR 6–15] vs 43 days [20–not reached]; p<0·0001; hazard ratio 3·56, 95% CI 1·65–7·69, after adjusting for age; figure). Figure Severe events in patients without cancer, cancer survivors, and patients with cancer (A) and risks of developing severe events for patients with cancer and patients without cancer (B) ICU=intensive care unit. In this study, we analysed the risk for severe COVID-19 in patients with cancer for the first time, to our knowledge; only by nationwide analysis can we follow up patients with rare but important comorbidities, such as cancer. We found that patients with cancer might have a higher risk of COVID-19 than individuals without cancer. Additionally, we showed that patients with cancer had poorer outcomes from COVID-19, providing a timely reminder to physicians that more intensive attention should be paid to patients with cancer, in case of rapid deterioration. Therefore, we propose three major strategies for patients with cancer in this COVID-19 crisis, and in future attacks of severe infectious diseases. First, an intentional postponing of adjuvant chemotherapy or elective surgery for stable cancer should be considered in endemic areas. Second, stronger personal protection provisions should be made for patients with cancer or cancer survivors. Third, more intensive surveillance or treatment should be considered when patients with cancer are infected with SARS-CoV-2, especially in older patients or those with other comorbidities.
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              Is Open Access

              Demographic science aids in understanding the spread and fatality rates of COVID-19

              Governments around the world must rapidly mobilize and make difficult policy decisions to mitigate the coronavirus disease 2019 (COVID-19) pandemic. Because deaths have been concentrated at older ages, we highlight the important role of demography, particularly, how the age structure of a population may help explain differences in fatality rates across countries and how transmission unfolds. We examine the role of age structure in deaths thus far in Italy and South Korea and illustrate how the pandemic could unfold in populations with similar population sizes but different age structures, showing a dramatically higher burden of mortality in countries with older versus younger populations. This powerful interaction of demography and current age-specific mortality for COVID-19 suggests that social distancing and other policies to slow transmission should consider the age composition of local and national contexts as well as intergenerational interactions. We also call for countries to provide case and fatality data disaggregated by age and sex to improve real-time targeted forecasting of hospitalization and critical care needs.
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                Author and article information

                Contributors
                eterpos@med.uoa.gr
                Journal
                Leukemia
                Leukemia
                Leukemia
                Nature Publishing Group UK (London )
                0887-6924
                1476-5551
                22 May 2020
                : 1-12
                Affiliations
                [1 ]ISNI 0000 0001 2155 0800, GRID grid.5216.0, Department of Clinical Therapeutics, School of Medicine, , National and Kapodistrian University of Athens, ; Athens, Greece
                [2 ]GRID grid.5963.9, Faculty of Freiburg, Hematology and Oncology Department, Interdisciplinary Cancer Center (ITZ) and Comprehensive Cancer Center Freiburg (CCCF), , University of Freiburg, ; Freiburg, Germany
                [3 ]ISNI 0000 0000 9965 1030, GRID grid.415967.8, Leeds Cancer Centre, , Leeds Teaching Hospitals National Health Service Trust and University of Leeds, ; Leeds, UK
                [4 ]ISNI 0000 0004 1789 4477, GRID grid.432329.d, Division of Hematology, University of Turin, , Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, ; Turin, Italy
                [5 ]GRID grid.452531.4, Cancer Research Unit, University Hospital of Salamanca, , Instituto de Investigación Biomédica de Salamanca (IBSAL), ; Salamanca, Spain
                [6 ]GRID grid.452531.4, Institute of Cancer Molecular and Cellular Biology (USAL-CSIC), Centre for Cancer Research (IBMCC), , Instituto de Investigación Biomédica de Salamanca (IBSAL), ; Salamanca, Spain
                [7 ]ISNI 0000 0004 1754 9227, GRID grid.12380.38, Department of Hematology, Cancer Center Amsterdam, Amsterdam UMC, , Vrije Universiteit Amsterdam, ; Amsterdam, The Netherlands
                [8 ]Genomics of Myeloma Laboratory, L’Institut Universitaire du Cancer Oncopole, Toulouse, France
                [9 ]ISNI 0000 0001 2155 4545, GRID grid.412684.d, Department of Hemato-Oncology, University Hospital Ostrava and Faculty of Medicine, , University of Ostrava, ; Ostrava, Czech Republic
                [10 ]ISNI 0000 0004 0646 7373, GRID grid.4973.9, Department of Hematology, , Copenhagen University Hospital, ; Rigshospitalet, Copenhagen Denmark
                [11 ]Wilhelminen Cancer Research Institute, c/o Department of Medical Oncology, Hematology and Palliative Care, Wilhelminenspital Wien, Austria
                [12 ]ISNI 0000 0004 0472 0371, GRID grid.277151.7, Department of Hematology, , University Hospital Hotel-Dieu, ; Nantes, France
                [13 ]ISNI 0000 0001 1378 7891, GRID grid.411760.5, Department of Internal Medicine II, , University Hospital of Würzburg, ; Würzburg, Germany
                [14 ]Clínica Universidad de Navarra-Centro de Investigación Médica Aplicada, Instituto de Investigación Sanitaria de Navarra, Centro de Investigación Biomédica en Red de Cáncer, Pamplona, Spain
                [15 ]ISNI 000000040459992X, GRID grid.5645.2, Department of Hematology, , Erasmus MC Cancer Institute, ; Rotterdam, The Netherlands
                Author information
                http://orcid.org/0000-0001-5133-1422
                http://orcid.org/0000-0003-2390-1218
                http://orcid.org/0000-0002-6328-9783
                http://orcid.org/0000-0002-2131-731X
                http://orcid.org/0000-0002-3302-8726
                Article
                876
                10.1038/s41375-020-0876-z
                7244257
                32444866
                bfd5befa-0d28-4164-af8c-af38d256fe3b
                © The Author(s), under exclusive licence to Springer Nature Limited 2020

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 29 April 2020
                : 6 May 2020
                : 13 May 2020
                Categories
                Review Article

                Oncology & Radiotherapy
                therapeutics,myeloma,infectious diseases
                Oncology & Radiotherapy
                therapeutics, myeloma, infectious diseases

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