Preliminary results from phase 2 of CC-92480- MM- 001: Mezigdomide plus dexamethasone in relapsed/refractory multiple myeloma (RRMM)

In phase 1 of CC-92480- MM- 001 (NCT03374085), the recommended phase 2 dose (RP2D) of mezigdomide plus dexamethasone (MEZI-d) was selected at 1 mg once daily for 21/28 days. Here we report preliminary results from the MEZI-d dose-expansion cohort in patients with heavily pretreated RRMM. Key eligibility criteria were: RRMM;>=3 prior lines of therapy;disease progression <=60 days of last myeloma therapy;refractoriness to lenalidomide/pomalidomide, a proteasome inhibitor, a glucocorticoid, and an anti-CD38 monoclonal antibody. Oral mezigdomide 1 mg was given on days 1-21 of each 28-day cycle, plus weekly dexamethasone (40 mg;20 mg if >75 years of age). Primary objective was to evaluate efficacy (overall response rate [ORR]);secondary objectives included safety/tolerability and additional efficacy assessments. Pharmacodynamics was an exploratory objective. As of 16/Sep/2022, 101 patients had received MEZI-d at the RP2D. Median age was 67 (range 42-85) years, median time since initial diagnosis was 7.4 (1.1-37.0) years;39.6% of patients had plasmacytomas and 37/101 patients had high-risk cytogenetics (56/101 not evaluable). Median number of prior regimens was 6 (3-15);prior therapies included stem cell transplantation (77.2%) and anti-BCMA therapy (29.7%). All patients were refractory to last myeloma regimen and triple-class refractory. Median follow-up was 7.5 (0.5-21.9) months, with a median of 4 (1-20) cycles;10.0% of patients continued treatment;progressive disease was the main reason for discontinuation (60.4%). ORR was 40.6% for all patients. Whilst data are not mature yet, median PFS was 4.4 (95% CI 3.0-5.5) months and median duration of response was 7.6 (95% CI 5.4-9.5) months. ORR was 30.0% in patients with plasmacytomas (N = 40) and 50.0% in patients with prior anti-BCMA therapy (N = 30). Ninety-one (91.1%) patients experienced a grade 3/4 treatment-emergent adverse event (TEAE). Most frequent hematologic grade 3/4 TEAEs were neutropenia (75.2%), anaemia (35.6%), and thrombocytopenia (27.7%);34.7% of patients had grade 3/4 infections, including grade 3/4 pneumonia (15.8%) and COVID-19 (7.0%). Occurrence of other grade 3/4 non-hematologic TEAEs was generally low. Due to TEAEs, 76.2% and 29.7% of patients had mezigdomide dose interruptions and reductions, respectively;90.1% of patients discontinued mezigdomide. Mezigdomide induced substrate degradation and increases in activated and proliferating T cells in patients, including those directly refractory to pomalidomide-based therapies. MEZI-d had a manageable safety profile with encouraging efficacy in patients with triple-class refractory RRMM, including patients with prior BCMA-targeted therapies. These results strongly support the continued development of mezigdomide in MM, and especially in combination.

Anthropological and social approach to death anxiety in the state security forces during the COVID-19 crisis

The recent events sweeping the planet in all their dimensions (environmental, health, economic, political) contribute to the fact that human beings find themselves devoid of personal resources to deal with them. During the first wave of the COVID-19 pandemic, professionals considered essential, such as the Security Forces and Corps, tried to provide the population with a certain degree of well-being and security. However, they paid the high price of many members of this group generating anxiety in the face of death, especially among those on the front line. This study, using a descriptive and mixed methodology, aims to determine the level of death anxiety in a large sample of these professionals (n = 1705) and to carry out an anthropological and social analysis of their perceptions of these events. The results have shown a significant presence of death anxiety in members of the Security Forces and Corps, especially during the pandemic's first phase, allowing for different anthropological interpretations.

Magnitude and Dynamics of the T-Cell Response to SARS-CoV-2 Infection and Vaccination

Background. T cells are central to the early identification and clearance of viral infections and support antibody generation by B cells, making them desirable for assessing the immune response to SARS-CoV-2 infection and vaccines. We combined 2 high-throughput immune profiling methods to create a quantitative picture of the SARS-CoV-2 T-cell response that is highly sensitive, durable, diagnostic, and discriminatory between natural infection and vaccination. Methods. We deeply characterized 116 convalescent COVID-19 subjects by experimentally mapping CD8 and CD4 T-cell responses via antigen stimulation to 545 Human Leukocyte Antigen (HLA) class I and 284 class II viral peptides. We also performed T-cell receptor (TCR) repertoire sequencing on 1815 samples from 1521 PCR-confirmed SARS-CoV-2 cases and 3500 controls to identify shared public TCRs from SARS-CoV-2-associated CD8 and CD4 T cells. Combining these approaches with additional samples from vaccinated individuals, we characterized the response to natural infection as well as vaccination by separating responses to spike protein from other viral targets. Results. We find that T-cell responses are often driven by a few immunodominant, HLA-restricted epitopes. As expected, the SARS-CoV-2 T-cell response peaks about 1-2 weeks after infection and is detectable at least several months after recovery. Applying these data, we trained a classifier to diagnose past SARS-CoV-2 infection based solely on TCR sequencing from blood samples and observed, at 99.8% specificity, high sensitivity soon after diagnosis (Day 3-7 = 85.1%;Day 8-14 = 94.8%) that persists after recovery (Day 29+/convalescent = 95.4%). Finally, by evaluating TCRs binding epitopes targeting all non-spike SARS-CoV-2 proteins, we were able to separate natural infection from vaccination with > 99% specificity. Conclusion. TCR repertoire sequencing from whole blood reliably measures the adaptive immune response to SARS-CoV-2 soon after viral antigenic exposure (before antibodies are typically detectable) as well as at later time points, and distinguishes post-infection vs. vaccine immune responses with high specificity. This approach to characterizing the cellular immune response has applications in clinical diagnostics as well as vaccine development and monitoring.

Severity of Covid-19 Clinical Outcomes and Mortality in Multiple Myeloma Patients over Year 1 of the Pandemic

Introduction In the first weeks of the Covid-19 pandemic when healthcare systems in many areas were overstretched, we documented that hospital mortality in multiple myeloma (MM) patients infected by Sars-Cov-2 was 50% higher than in age matched Covid-19 patients without cancer. In the following months, the pressure on healthcare systems in Spain continued although it did not reach the extreme levels of the first weeks of the pandemic. In this study, we proposed to determine if the severity of Covid-19 outcomes in MM patients has changed over the first year of the pandemic. Patients and methods The Spanish MM Collaborative Group (Pethema-GEM) conducted a survey at national level on plasma cell disorder patients infected by SARS-Cov-2 between March 2020 and February 2021. Sixty-six (69%) out of 96 contacted healthcare centers, from all 17 regions in Spain, reported 502 patients. Data on Covid-19 acute and post-acute phase outcomes (hospitalization, oxygen requirements, severity of symptoms and mortality) were reported first in May 2020 (Martinez-Lopez et al, BCJ 2021) and updated in February 2021. In this study, we compared outcome occurrence between two study periods: P1, a period of extreme stress for the healthcare system in Spain, from March to mid-June 2020;and a second period, P2, up to mid-February 2021 with a sustained but lower burden on the national health care system. Results Among the 451 patients with plasma cell disorders and a Sars-Cov-2 infection documented with an rRT-PCR positive test, 377 (84%) were MM patients, 15 SMM (3%), 40 MGUS (9%) and 19 amyloidosis (4%). The number of MM weekly reported cases was 57% (95%CI, 48-65) lower in P2 (188 cases in 35 weeks) compared to P1 (189 cases in 15 weeks), p<0.001. The mean (SD) age and the proportion of men did not differ between P1 and P2, respectively 69.8 (10.9) vs 68.6 (11.0) years, p=0.6, and 53.3% vs 59.6%, p=0.2. MM patients with active or progressive disease at time of Covid-19 diagnosis were 24% in P1 and 34% in P2, p=0.05;patients on active treatment were more frequent in P1, 89%, than in P2, 79%, p=0.01. MM treatment was withheld in 78% and 82% of patients, p=0.4. Covid-19 treatment changed over time: MM inpatients received more remdesivir and corticoids in the second period (3% vs 31% p<0.001, and 49% vs 73%, p<0.001, respectively). In P1, 90% of the reported MM patients were hospitalized compared to 71% in P2, p<0.001. Thirty-one and 41% of patients did not require oxygen support during P1 and P2, respectively;non-invasive ventilation in 19% and 14%, and mechanical ventilation in 7% and 8%, p=0.12. Overall, acute clinical Covid-19 severity was reduced from P1 to P2: 75% to 51%, p<0.001: moderate/severe pneumonia was reduced from 68% to 36%, p<0.001 but severe distress syndrome increased from 7% to 15%, p=0.03. However, mortality in all reported patients was 30.7% in P1 vs 26.1% in P2, p=0.3;and no differences in mortality were observed in hospitalized patients, 32.2% in P1 and 35.3% in P2, p=0.6. We performed a multivariable adjustment with the predictors identified in our previous study (BCJ 2021) and confirmed that inpatient mortality was similar in both study periods, odds ratio (OR) 0.99 (95%CI 0.59-1.66). Independently of the study period, an increased mortality was observed in men (OR 1.81, 1.08-3.05), patients over 65 (OR 2.40, 1.33-4.36), and patients with active or progressive disease (OR 2.12, 1.24-3.62). The severity of Covid-19 clinical outcomes -besides mortality, was associated with increased age but not with active or progressive disease. Conclusions Although COVID-19 clinical severity has decreased over the first year of the pandemic in multiple myeloma patients, mortality remains high with no change between the initial weeks of the pandemic and the following months. Prevention and vaccination strategies should be strengthened in this vulnerable population, particularly in patients with active or progressive disease at time of Covid-19 diagnosis. Disclosures: Martínez-López: Janssen, BMS, Novartis, Incyte, Roche, GSK, Pfi er: Consultancy;Roche, Novartis, Incyte, Astellas, BMS: Research Funding. Mateos: Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees;Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees;Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees;Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees;Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees;Sea-Gen: Honoraria, Membership on an entity's Board of Directors or advisory committees;AbbVie: Honoraria;Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees;Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees;Celgene - Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Bluebird bio: Honoraria;GSK: Honoraria;Oncopeptides: Honoraria. López-Muñoz: Amgen: Consultancy. Sureda: GSK: Consultancy, Honoraria, Speakers Bureau;Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Roche: Other: Support for attending meetings and/or travel;Mundipharma: Consultancy;Bluebird: Membership on an entity's Board of Directors or advisory committees;Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;MSD: Consultancy, Honoraria, Speakers Bureau;BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Speakers Bureau;Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding, Speakers Bureau. Rosinol: Janssen, Celgene, Amgen and Takeda: Honoraria. Lahuerta: Celgene, Takeda, Amgen, Janssen and Sanofi: Consultancy;Celgene: Other: Travel accomodations and expenses. San-Miguel: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Karyopharm, Merck Sharpe & Dohme, Novartis, Regeneron, Roche, Sanofi, SecuraBio, Takeda: Consultancy, Other: Advisory board.

Communication and Cultural Approach to the Situation of Health Professionals in the Face of the COVID-19 Pandemic

Introduction. The beginning of the third decade of the 21st century will be remembered for the COVID-19 pandemic and the health crisis it has produced, altering different systems such as the cultural, political, economic, media and communication systems. From the anthropology of health, the interconnections between the health system, communication, and culture can be observed, visible and indivisible by the many edges that coexist and conform to a field of own analysis. Methodology: This empirical research has been developed from a qualitative perspective through 40 anonymous semi-structured interviews in Spain during the height of the health crisis - in the state of alarm - and investigates how this pandemic affected health professionals during the first wave of the pandemic. They were the fundamental barrier to deal with the SARS-CoV-2 coronavirus, and they carried out their work in highly precarious conditions, with hardly any personal protection equipment, sufficient human resources, and the essential infrastructures to care for patients. Results/Discussion: The study focuses on three dimensions: (a) the cultural aspects that impregnate the professional activity of the health workers, (b) the emotional aspects in the development of the same about the processes of mourning and death from its symbolic components, and (c) the perceptions it has of the health management carried out by the public response. Conclusions: The results describe the extreme situation these professionals in a health crisis without precedent in decades, reflecting a new anthropological and sociological scenario.

Poor Outcome of Patients with COVID-19 after CAR T-Cell Therapy for B-Cell Malignancies: Results from a Multicenter Study on Behalf of the European Society for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party and the European Hematology Association (EHA) Lymphoma Group

Background The ongoing Coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is having an enormous impact on society worldwide and is especially posing a threat to health in vulnerable patients, such as patients with immune deficiencies. It is expected that patients who received Chimeric Antigen Receptor T-cell (CAR T-cell) therapy for hematologic malignancies are at risk for poor outcomes after COVID-19 due to their severely immunocompromised state caused by prior cumulative immunochemotherapy, on-target/off-tumor B-cell depletion, hypogammaglobulinemia and ongoing cytopenias. Current data are limited to small case series and case reports. This study describes the clinical characteristics and outcomes of CAR T-cell therapy recipients after developing COVID-19 in the largest cohort to date. Methods In response to the COVID-19 pandemic, the European Society for Blood and Marrow Transplantation (EBMT) developed a special COVID-19 report form to capture data from all patients with COVID-19 after treatment with CAR T-cell therapy for hematologic malignancies. Only PCR positive SARS-CoV-2 diagnosed patients before June 1 st, 2021 were included. The aim of this study was to describe the clinical course after COVID-19 diagnosis and evaluate overall survival. Overall survival probabilities were calculated using the Kaplan Meier method. Factors associated with mortality after COVID-19 diagnosis were examined using a Cox proportional hazard model. Results A total of 57 patients from 11 countries were reported to the EBMT. One patient with incomplete data at diagnosis and without any follow up information had to be excluded from the analysis. The median age of these 56 patients was 57.7 years (min-max 5.2 - 72.8) including 55 adults and one child. Of these patients, 32 were male. CAR T-cell therapy was given to 46 patients with B-cell-non-Hodgkin lymphoma, 7 patients with B-cell acute lymphoblastic leukemia, and 3 patients with multiple myeloma. The median time from CAR T-cell infusion to COVID-19 diagnosis was 7.4 months (min-max 0.03 - 25.3). At the time of COVID-19 diagnosis, 62.5% of patients were in complete remission, 12.5% of patients had a partial response and 25% of patients had relapsed/refractory disease. Forty-five patients (80%) were admitted to hospital (median 26,5 days, min-max 3-171) due to COVID-19. Of the admitted patients, 24 (53%) needed oxygen support. Twenty-two (49%) patients were admitted to the intensive care unit (median 14 days, min - max 2-65) and 16 (73%) of these patients received invasive ventilation. At the time of analysis, 25 of the 56 patients had died (44.6%), most (23/25) due to COVID-19, resulting in a COVID-19 attributable mortality rate of 41%. The Kaplan-Meier estimate of overall survival is shown in Figure 1. The median follow-up from COVID-19 diagnosis was 20.9 weeks. In 1 of the 32 alive patients there was no resolution of COVID-19 at the time of analysis. In multivariate analysis, older age (hazard ratio (HR) 1.50, 95% CI 1.11-2.03, p=0.009) and comorbidities (HR 2.56, 95% CI 1.05-6.23, p=0.001) had a negative impact on overall survival. Better performance status at time of admission (HR 0.72, 95% CI 0.59-0.88, p=0.038) had a positive impact on overall survival. Sex, time from CAR T-cell therapy to COVID-19 diagnosis, disease remission status and the occurrence of neurotoxicity or cytokine release syndrome after CAR T-cell infusion did not have a significant effect on overall survival in the multivariate analysis. Conclusion Patients with COVID-19 after B-cell-targeted CAR T-cell therapy have a very poor outcome. As it remains uncertain whether currently applied vaccination strategies against SARS-CoV-2 are effective after CAR T-cell therapy, vaccination of health-care personnel and family members in combination with protective measures against viral exposure are likely to play the most important role in protecting this vulnerable group of patients. Better treatment strategies are urgently needed. [Formula present d] Disclosures: Ljungman: OctaPharma: Other: DSMB;Enanta: Other: DSMB;Janssen: Other: Investigator;Takeda: Consultancy, Other: Endpoint committee, speaker;AiCuris: Consultancy;Merck: Other: Investigator, speaker. De La Camara: IQONE: Consultancy;Roche: Consultancy. Ortiz-Maldonado: Kite, Novartis, BMS, Janssen: Honoraria. Barba: Novartis: Honoraria;Gilead: Honoraria;BMS: Honoraria;Amgen: Honoraria;Pfizer: Honoraria. Kwon: Novartis, Celgene, Gilead, Pfizer: Consultancy, Honoraria. Sesques: Novartis: Honoraria;Chugai: Honoraria;Kite, a Gilead Company: Honoraria. Bachy: Kite, a Gilead Company: Honoraria;Novartis: Honoraria;Daiishi: Research Funding;Roche: Consultancy;Takeda: Consultancy;Incyte: Consultancy. Di Blasi: Kite, a Gilead Company: Consultancy, Honoraria;Novartis: Consultancy, Honoraria;Janssen: Consultancy, Honoraria. Thieblemont: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding;Gilead Sciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees;Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Hospira: Research Funding;Bayer: Honoraria;Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses. Mutsaers: BMS: Consultancy;AstraZeneca: Research Funding. Nicholson: Kite, a Gilead Company: Other: Conference fees, Speakers Bureau;Novartis: Consultancy, Other: Conference fees;BMS/Celgene: Consultancy;Pfizer: Consultancy. Martínez-López: Janssen, BMS, Novartis, Incyte, Roche, GSK, Pfizer: Consultancy;Roche, Novartis, Incyte, Astellas, BMS: Research Funding. Ribera: NOVARTIS: Consultancy, Speakers Bureau;TAKEDA: Consultancy, Research Funding, Speakers Bureau;ARIAD: Consultancy, Research Funding, Speakers Bureau;SHIRE: Consultancy, Speakers Bureau;AMGEN: Consultancy, Research Funding, Speakers Bureau;Pfizer: Consultancy, Research Funding, Speakers Bureau. Sanderson: Kite, a Gilead Company: Honoraria;Novartis: Honoraria. Bloor: Kite, a Gilead Company: Honoraria;Novartis: Honoraria. Ciceri: IRCCS Ospedale San Raffaele: Current Employment. Ayuk: Novartis: Honoraria;Janssen: Honoraria;Takeda: Honoraria;Mallinckrodt/Therakos: Honoraria, Research Funding;Gilead: Honoraria;Miltenyi Biomedicine: Honoraria;Celgene/BMS: Honoraria. Kröger: Novartis: Research Funding;Riemser: Honoraria, Research Funding;Sanofi: Honoraria;Neovii: Honoraria, Research Funding;Jazz: Honoraria, Research Funding;Gilead/Kite: Honoraria;Celgene: Honoraria, Research Funding;AOP Pharma: Honoraria. Kersten: Celgene: Research Funding;Miltenyi Biotec: Consultancy, Honoraria, Other: Travel support;Roche: Consultancy, Honoraria, Other: Travel support, Research Funding;BMS/Celgene: Consultancy, Honoraria;Takeda: Research Funding;Novartis: Consultancy, Honoraria, Other: Travel support;Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel support, Research Funding. Mielke: DNA Prime SA: Speakers Bureau;Im unicum: Other: Data safety monitoring board;Novartis: Speakers Bureau;Miltenyi: Other: Data safety monitoring board;Gilead/KITE: Other: Travel support, Expert panel;Celgene/BMS: Speakers Bureau.

Acute and Post-Acute COVID-19 Severity and Mortality in Patients with Hematologic Malignancies: A Population-Based Registry Study

Introduction: The severity of acute clinical outcomes and mortality in hematologic malignancy (HM) patients infected by SARS-CoV-2 was exhaustively documented in the first weeks of the pandemic. A consistent increased mortality compared to non-cancer patients was observed across studies. In this study we aimed to estimate survival in COVID-19 HM patients by type of malignancy, to describe acute and post-acute clinical outcomes, and to compare outcomes in early and later pandemic periods. Methods: In this population-based registry study sponsored by the Madrid Society of Hematology (Asociación Madrileña de Hematología y Hemoterapia), we collected de-identified data on clinical characteristics, treatment and acute and post-acute outcomes in adult patients with hematologic malignancies and confirmed SARS-CoV-2 infection within the Madrid region of Spain. Our case series included all eligible patients admitted to 26 regional health service hospitals and 5 private healthcare centers between February 28, 2020 and February 18, 2021 with a coverage of 98% on a population of 6.6 million inhabitants. The study outcomes were all-cause mortality, severity of disease (WHO), oxygen support, ICU admission, and follow-up symptoms and signs and complications. Survival probabilities were estimated with the actuarial method and reported overall and stratified by type of malignancy and for two study periods (early cohort,-COVID-19 diagnosis from February 28 to 31 May, 2020, and later cohort, up to February 18, 2021). Results: Of the 1408 patients reported to the HEMATO-MADRID COVID-19 registry, 1166 were included in the present analyses;839 (72%) had a lymphoid malignancy, including 325 (28%) with non-Hodgkin lymphoma, 50 (4%) with Hodgkin lymphoma and 263 (23%) with multiple myeloma;and 327 (28%) had a myeloid malignancy, including 115 (10%) with myelodysplastic syndrome, 92 (8%) with acute myeloid leukemia (AML) and 87 (7%) with Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms. Overall COVID-19 clinical severity was classified as critical in 19% of patients, severe in 36%, moderate in 22%, and mild in 22%;10% were admitted to an ICU;8% were on mechanical ventilation and 19% on noninvasive ventilation. Mild disease increased between early and later period from 15% to 38% of patients;severe disease decreased from 42% to 24%, p<0.001. COVID-19 treatment with steroids increased from 38% to 59%, p<0.001. At follow-up, 22% reported persistent symptoms related to COVID-19 at 2 months, 16% at 4 months and 14% at 6 months. 381 of 1166 (33%) patients died. Overall 30-day survival was 68%;2 and 3-month overall survival probabilities were 56% and 53%, respectively. Survival was more favorable for patients with myeloproliferative neoplasms (82%, 69% and 65% at 30-days, 2 and 3 months, respectively) than for those with lymphoid malignancies (68%, 56% and 54%) or myelodysplastic syndrome/acute myeloid leukemia (61%, 51%, 46%), p=001. 285 (37%) patients died in the early period vs 96 (24%) in the later, p<0.001, but median (interquartile range) follow-up time was much higher in the early vs later, 45 (20-116) days vs. 26 (11-86), respectively. Overall survival was not different between periods, p=0.5 (hazard ratio [95%C], 0.93 [0.73-1.17]). In the later cohort, 30 and 60-day survival probabilities were 71% and 56% vs. 67% and 56% in the early cohort Conclusions. A population-based registry in Spain provided strong evidence that although COVID-19 severity decreased over year 1 of the pandemic, mortality remained high, and survival was stable over time in the group of patients with hematological malignancy infected by SARS-Coc-2. A relevant proportion of the infected patients (1 in 6) referred persistent symptoms attributable to COVID-19. The improved clinical management of severe COVID-19 in non-cancer patients that followed the dissemination of evidence-based recommendations did not translate in more favorable survival in patients with hematological malignancies. Research is needed to address the specific characteristics nd improve the clinical management of this vulnerable population. Disclosures: Martinez-Lopez: Novartis: Consultancy, Speakers Bureau;BMS: Consultancy, Research Funding, Speakers Bureau;Janssen: Consultancy, Speakers Bureau;Incyte: Consultancy, Research Funding, Speakers Bureau;Roche: Consultancy, Research Funding, Speakers Bureau;Astellas: Research Funding, Speakers Bureau. Jiménez-Yuste: Pfizer: Consultancy, Honoraria, Research Funding;Grifols: Consultancy, Honoraria, Research Funding;CSL Behring: Consultancy, Honoraria, Research Funding;Sanofi: Consultancy, Honoraria, Research Funding;Bayer: Consultancy, Honoraria, Research Funding;NovoNordisk: Consultancy, Honoraria, Research Funding;BioMarin: Consultancy;Sobi: Consultancy, Honoraria, Research Funding;Octapharma: Consultancy, Honoraria, Research Funding;Takeda: Consultancy, Honoraria, Research Funding;F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding. Kwon: Gilead: Honoraria.

Impact of COVID-19 in patients with multiple myeloma based on a global data network.

The COVID-19 pandemic has represented a major cause of morbidity/mortality worldwide, overstressing health systems. Multiple myeloma (MM) patients show an increased risk for infections and they are expected to be particularly vulnerable to SARS-CoV-2 infection. Here we have obtained a comprehensive picture of the impact of COVID-19 in MM patients on a local and a global scale using a federated data research network (TriNetX) that provided access to Electronic Medical Records (EMR) from Health Care Organizations (HCO) all over the world. Through propensity score matched analyses we found that the number of new diagnoses of MM was reduced in 2020 compared to 2019 (RR 0.86, 95%CI 0.76-0.96) and the survival of newly diagnosed MM cases decreased similarly (HR 0.61, 0.38-0.81). MM patients showed higher risk of SARS-CoV-2 infection (RR 2.09, 1.58-2.76) and a higher excess mortality in 2020 (difference in excess mortality 9%, 4.4-13.2) than non-MM patients. By interrogating large EMR datasets from HCO in Europe and globally, we confirmed that MM patients have been more severely impacted by COVID-19 pandemic than non-MM patients. This study highlights the necessity of extending preventive measures worlwide to protect vulnerable patients from SARS-CoV-2 infection by promoting social distancing and an intensive vaccination strategies.

P-137: ITHACA, a randomized multicenter phase 3 study of Isatuximab in combination with Lenalidomide and Dexamethasone in high-risk smoldering Multiple Myeloma: safety run-in preliminary results

Background: High-risk smoldering multiple myeloma (HR-SMM) is associated with a greater risk of progression to symptomatic disease, suggesting the need for early, efficacious therapeutic interventions to improve outcomes. The ongoing, randomized Phase 3 ITHACA study (NCT04270409) is evaluating efficacy and safety of the anti-CD38 monoclonal antibody isatuximab (Isa) in combination with lenalidomide (R) and dexamethasone (d) (Isa-Rd) vs Rd in patients (pts) with HR-SMM. We report here preliminary results from the safety run-in part of this trial. Methods: The primary objective was to confirm the recommended dose of Isa in combination with Rd. Pts were eligible if diagnosed with SMM within 5 years and HR-SMM defined by the Mayo ‘20-2-20’ and/or updated PETHEMA model criteria. Minimal residual disease and imaging by MRI and low-dose whole-body CT/PET-CT will be assessed at fixed time points. Results: As of April 12, 2021, 23 pts (median age, 63 [28–85] years;median time from initial diagnosis, 1.14 [0.1–5.2] years) had received Isa 10 mg/kg once weekly then biweekly (QW-Q2W) in combination with Rd. The median number of cycles was 7 (range, 4–10) and median duration of treatment exposure was 29.7 (range, 16.0–38.0) weeks. Two pts met the Mayo clinical model criteria, 13 pts the PETHEMA model criteria, and 8 pts both models’ criteria for HR-SMM. No pt presented with focal lesions at baseline. Seven (30.4%) pts developed 8 grade ≥3 non-hematologic treatment-emergent adverse events (TEAEs): COVID-19 pneumonia, insomnia (2 each), papular rash, muscle spasm, retinal detachment and hyperglycemia (1 each);no pt experienced a grade 5 TEAE and no pt discontinued treatment due to a TEAE. Serious TEAEs were COVID-19 pneumonia (n=2, grade ≥3) and pneumonia, musculoskeletal chest pain and pyrexia (n=1 each, grade <3). The most common, mostly grade 1–2 TEAEs were insomnia (39%) and constipation, headache, and peripheral edema (22% each). Infusion reactions were reported in 2 pts (8.7%) (grade 2, infusion day 1/cycle 1). By laboratory results, no grade 3–4 anemia or thrombocytopenia was observed;grade 3 neutropenia was reported in 5 pts (21.7%), with no grade 4. Isa exposure and CD38 receptor occupancy were in accordance with other MM studies, reaching target saturation in bone marrow plasma cells. The overall response rate was 86.9%;21.7%, 17.4%, and 4.3% of pts have so far achieved very good partial response (VGPR), complete response (CR) and stringent CR (sCR), respectively. Conclusions: Addition of Isa 10 mg/kg QW-Q2W to Rd was associated with a favorable safety profile in pts with HR-SMM, which compares well with Rd literature data in the same patient population. Isa-Rd has shown encouraging preliminary efficacy (21.7% sCR/CR and 43.4% ≥VGPR rates) in pts with HR-SMM. These results confirm the recommended dose of Isa for the randomized part of the Phase 3 ITHACA study, which will further evaluate efficacy and safety of Isa-Rd in HR-SMM. Funding: Sanofi.

MEDIIK: Design and Manufacturing of an Emergency Ventilator against COVID-19 Pandemic

Herein we describe the modular design and manufacturing of an emergency ventilator based on cyclical compression of a resuscitation bag to face the COVID-19 pandemic. This was done to mitigate the staggering conditions to supply these medical devices under challenging scenarios of need and logistics. The design is based on international standards and commissions for medical electrical equipment, particular requirements for basic safety, electromagnetic compatibility, and essential performance of critical care and emergency ventilators. The modular design is capable of providing four ventilation modes: volume/pressure mandatory ventilation and volume/pressure assisted ventilation. After testing with artificial lungs, calibration, and validation instruments it was found that the main ventilation parameters achieved are: maximum tidal volume of 700 mL, maximum pressure of 50 cmH2O, inspiration/expiration ratio up to 1:4 at 30 breaths per minute. The MEDIIK designation is derived from the mayan word ik' which means wind. © 2021 ACM.

Social networks consumption and addiction in college students during the COVID-19 pandemic: educational approach to responsible use

Within the framework of digital sustainability, the increase in Internet consumption, and especially online social networks, offers social benefits, but is not without its drawbacks. For example, it can lead to psychological and/or psychiatric disorders in some people. Numerous researches are highlighting the similarities of these addictions with the consumption of toxic substances. University students are heavy users of the Internet and, in certain situations, addiction to online social networks can be the result of depression, harassment, and anxiety, among others, affecting their daily life, including their academic responsibilities. In recent months, an anomaly has occurred that may have contributed to intensifying this problem, namely the confinement produced by the COVID-19 pandemic, which has affected the whole world to a greater or lesser extent. In this cross-sectional study, with a descriptive and quantitative methodology, students from 14 Spanish universities were investigated in the first wave of the COVID-19 pandemic in order to understand the effects of this situation on the problem described. The results show a high consumption of social networks during that time, with significant incidences of addiction. In parallel, the presence of comorbidity has been determined. In this scenario, it would be necessary to implement university educational programs to redirect these addictive behaviors, as well as preventative recommendations and actions to minimize negative impacts. This is a major problem that is growing, exacerbated by the global pandemic produced by the SARS-CoV-2 coronavirus. Situations of this gravity call for the development of preventive and educational measures for the responsible and sustainable use of ICT.

Burnout among direct-care workers in nursing homes during the covid-19 pandemic in spain: A preventive and educational focus for sustainable workplaces

Due to their continuous contact with pain and death, healthcare workers have one of the most stressful professions. Pain and death are more common in nursing homes. During the health crisis associated with COVID-19, these work centers have been characterized as spaces of high vul-nerability to infection for the elderly, with a high mortality rate. This research aims to determine how the health crisis associated with COVID-19 has influenced healthcare professionals working in nursing homes for the elderly. Using a quantitative and cross-sectional method, the research was developed in residential centers in the Region of Murcia (Spain) during the second wave of the pandemic. A survey design based mainly on the Maslach Burnout Inventory (MBI) was employed. MBI measures three subscales: emotional burnout, depersonalization, and self-fulfillment. The results show that 6.4% of the respondents were burned out, 53.8% of the participants were emotion-ally exhausted, 35.1% were found to suffer from depersonalization, and in the case of personal de-velopment, the respondents showed a low level of 15.6%. This study shows the need to consider the establishment, in the academic environment, of training programs for health professionals related to coping with, managing, and identifying stress, especially in adverse circumstances. Similarly, in the professional field, it is necessary to develop strategies to prevent stress and anxiety in the work-place. The development of training programs for this purpose is essential for achieving a sustainable work context. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Approach to long-term care during the peak of COVID-19 in the region of Murcia

The global health crisis resulting from the COVID-19 pandemic is affecting all spheres of society, including long-term care. During the most critical weeks of the first wave of the pandemic in Spain, the difficulties for caregivers have increased to those traditionally existing, characterized by: the difficult fit between work and care, the invisibility and lack of social recognition of their work, the development of care in precariousness and lack of social protection, low wages, burnout syndrome, etc. The general objective of this study is to describe how care work was developed during the peak of the pandemic during the first wave in Spain. In this context, exploratory, descriptive, and transversal research has been developed from an eminently quantitative method through the technique of the survey during April 2020. The major results show that the care work has meant an important overload for the caregivers, increasing the hours they spend on care, affecting their health and their level of emotional fatigue and anxiety before the processes of dying of others. © 2021 Fundacion para la Investigacion Social Avanzada. All rights reserved.

Addictions in Spanish college students in confinement times: Preventive and social perspective

Diverse studies have shown that a significant percentage of the Spanish university population suffers from different addictions. They are both a personal and public health problem if there is not a greater awareness of the risks involved and if the appropriate prevention measures are not taken, among them educational ones. In this context, a descriptive and explanatory cross-sectional study was conducted during the first half of June 2020, coinciding with the period of confinement that occurred in Spain during the first wave of the COVID-19 pandemic. Given that this is such an exceptional time, the main objective of this study was to obtain information especially on students’ substance consumption and possible addictions at this time. Knowing the specific situation of this problem in that specific situation may allow for comparative studies in the future. The sample was composed of 310 university students from 14 Spanish universities. The instrument used in the research was the ASSIST questionnaire, developed by the WHO for the detection of alcohol, tobacco, and substance consumption. As result, a moderate and high risk was observed mainly in the following substances: alcohol (36.2%), tobacco (33.2%), cannabis (22.9%), and sedatives (10.3%). Through the logistic regression of the set of drugs, it has been proven that, on the one hand, the addiction to cocaine and sedatives in the family environment and age, on the other hand, are the main predictive variables of drug consumption. The existence of polysubstance abuse was also determined. These data show the need for educational bodies and university institutions to promote awareness, sensitization, and health education programs to deal with this important problem, especially in extraordinary situations, such as the one referred to, which could increase this consumption. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.