PRIOR EXPOSURE TO IMMUNOSUPPRESSIVE AGENTS AND COMORBIDITIES ARE ASSOCIATED WITH WORSE OUTCOMES OF SARS-COV2 INFECTION IN PH-NEG CHRONIC MYELOPROLIFERATIVE NEOPLASMS: RESULTS OF EPICOVIDEHA SURVEY

Background: Philadelphia-negatie chronic myeloproliferatie neoplasms (MPN) typically incur high rates of thrombosis and infections and cytoreductie drugs may modulate such risks. Aims: The present analysis aims at assessing the seerity and outcomes of MPN facing coronairus disease 2019 (COVID-19). Hence, we aimed to assess the impact of immunosuppressie agents and comorbidity burden in COVID- 19 outcome. Methods: The EPICOVIDEHA registry is an online surey (www.clinicalsureys.net) that has collected since April 2020 until January 2022 5,445 cases of COVID-19 in indiiduals with baseline haematological malignancies (Salmanton-García et al, 2021 Hemasphere) The surey is promoted by the European Hematology Association - Infectious Diseases Working Party (EHA-IDWP) and has been approed centrally by the Institutional Reiew Board and Ethics Committee of Fondazione Policlinico Uniersitario A. Gemelli - IRCCS - Uniersità Cattolica del Sacro Cuore, Rome, Italy (Study ID: 3226). Results: Oerall, 308 patients (5.6%) with MPN were obsered for a median of 102 days (IQR: 21-223, range 22-97) after COVID-19 diagnosis. Median age at infection was 69 years (IQR: 58-77, range 22-97) and at least one comorbidity was reported from most of the indiiduals (62.6%, n = 193). A large portion of patients had a history of cardiopathy (n=109, 35.4%), diabetes (n=40, 15.9%), or chronic pulmonary disease (n=44, 14.3%). Myelofibrosis (MF) (n=140, 45.4%) was the most prealent baseline malignancy, with 18 MF patients (12.9%) reporting 3 or more comorbidities. Out of the whole cohort, 72 patients (42.8% of MF) receied immunosuppressige therapies including steroids, immunomodulatory drugs (IMiDs) or JAK-inhibitors. Hospitalization and consecutie admission to intensie care unit was required for 187 (60.7%) and 45 (24%) patients, respectiely. At multiariate logistic regression, Hospital admission was predicted by age >70 years (OR 2.809;95% CI 1.651-4.779), exposure to immunosuppressie therapies (OR 2.802;95% CI 1.5380-5.103) and comorbidity burden. During the study follow-up (median 101 days;range 21-222) 84 patients deceased after a median time of 14 days (IQR: 8-49, range 0-457) since COVID-19 diagnosis. The fatality rate (FR) decreased from 40.3% (50 out of 124) in the first two quarters of year 2020 to 15.8% (3 out of 19) in the first two quarters of year 2021 (p<0.05). Death was principally attributable to COVID-19 in 58 patients (69.0%) and contributable by COVID-19 in 15 (17.9%). FR was particularly high (54 out of 140, 38.6%) in MF patients and in patients receiing immunosuppressie agents (32 out of 86, 37%). Moreoer, FR increased from 13.0% in indiiduals with no comorbidity to 36.0% and 62.1% in those with >2 or >3 comorbidities, respectiely. More specifically, three comorbidities independently increased the FR: chronic cardiopathy (HR 1.653;95%CI 1.017-2.687), chronic pulmonary disease (HR 1.847;95% CI 1.097-3.109), and diabetes mellitus (HR 1.712;95% CI 1.006-2.914). A heay comorbidity burden, namely 3 or more comorbidities (HR 2.956;95% CI 1.403-6.227), adanced age, namely >70 years (HR .809;95% CI 1.651-4.779), myelofibrosis (HR 2.501;95% CI 1.384-4.519), and ICU admission (HR 2.669;95% CI 1.641-4.342) independently predicted FR. (MF) (n=140, 45.4%) was the most prealent baseline malignancy, with 18 MF patients (12.9%) reporting 3 or more comorbidities. Out of the whole cohort, 72 patients (42.8% of MF) receied immunosuppressige therapies including steroids, immunomodulatory drugs (IMiDs) or JAK-inhibitors. Hospitalization and consecutie admission to intensie care unit was required for 187 (60.7%) and 45 (24%) patients, respectiely. At multiariate logistic regression, Hospital admission was predicted by age >70 years (OR 2.809;95% CI 1.651-4.779), exposure to immunosuppressie therapies (OR 2.802;95% CI 1.5380-5.103) and comorbidity burden. During the study follow-up (median 101 days;range 21-222) 84 patients deceased after a median time of 14 days (IQR: 8-49, range 0-457) since COVID-19 diagnosis. The fatality rate (FR) dec eased from 40.3% (50 out of 124) in the first two quarters of year 2020 to 15.8% (3 out of 19) in the first two quarters of year 2021 (p<0.05). Death was principally attributable to COVID-19 in 58 patients (69.0%) and contributable by COVID-19 in 15 (17.9%). FR was particularly high (54 out of 140, 38.6%) in MF patients and in patients receiing immunosuppressie agents (32 out of 86, 37%). Moreoer, FR increased from 13.0% in indiiduals with no comorbidity to 36.0% and 62.1% in those with >2 or >3 comorbidities, respectiely. More specifically, three comorbidities independently increased the FR: chronic cardiopathy (HR 1.653;95%CI 1.017-2.687), chronic pulmonary disease (HR 1.847;95% CI 1.097-3.109), and diabetes mellitus (HR 1.712;95% CI 1.006-2.914). A heay comorbidity burden, namely 3 or more comorbidities (HR 2.956;95% CI 1.403-6.227), adanced age, namely >70 years (HR .809;95% CI 1.651-4.779), myelofibrosis (HR 2.501;95% CI 1.384-4.519), and ICU admission (HR 2.669;95% CI 1.641-4.342) independently predicted FR. Summary/Conclusion: COVID-19 infection led to a particularly dismal outcome in patients exposed to immunosuppressie agents and in those with chronic heart or pulmonary diseases, or diabetes. These data allow to tailor future strategies for preenting seere COVID-19 in MPN patients. (Table Presented).

EFFECT OF ANTI-SPIKE NEUTRALIZING MONOCLONAL ANTIBODIES ON COVID-19 PROGRESSION AND TIME TO VIRAL CLEARANCE IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES AND SARS-COV-2 INFECTION: THE GIMEMA EXPERIENCE

Background: Patients with hematological malignancies (HM) infected with SARS-CoV-2 hae a higher risk of deeloping seere coronairus disease (COVID-19) with consequent death, due to immune system impairment. Anti-spike Neutralizing Monoclonal Antibodies (nMoAbs) are indicated for the treatment of paucisymptomatic COVID-19 patients, but eidence of safety and efficacy among HM subjects is still lacking. Aims: To assess the efficacy of different nMoAbs approed by Agenzia Italiana del Farmaco (AIFA) on HM patients affected by paucisymptomatic SARS-COV-2. Methods: Multicenter retrospectie obserational study at ten sites in Italy, which enrolled consecutie patients with SARS-CoV-2 infection and treated with nMoAbs from February 2020 to December 2021. Only HM subjects on treatment or in disease remission within 6 months from treatment discontinuation with paucisymptomatic SARSCOV- 2 infection were included. nMoAbs approed by AIFA include Bamlaniimab, Bamlaniimab/Eteseimab, Casiriimab/Imdeimab, Sotroimab, and Regdanimab. The primary endpoint was to assess the time to SARS-CoV- 2 molecular swab negatiization. A comparison to an historical control not receiing nMoAbs was assessed. Secondary endpoints consisted in ealuation of Hospitalization rate due to COVID-19, including intensie care unit (ICU) admission rate due to respiratory failure, and safety assessment. Results: Oerall 51 HM patients (median age 62 years;35% women) were ealuated. Seenteen of them had non- Hodgkin lymphomas, 9 multiple myeloma, 6 chronic lymphocytic leukemia, 6 acute myeloid leukemia, 3 Hodgkin lymphoma, 2 acute lymphoblastic leukemia, 2 myeloproliferatie neoplasm, 1 Waldenstrom macroglobulinemia and 5 had other HM diagnosis. Thirty-six patients were on actie treatment, whereas 11 had completed their therapies within 6 months from nMoAbs administration, for 4 patients data were missing. In 7 subjects the last treatment was chemotherapy, in 19 immunotherapy with or without chemotherapy, in 9 target therapy, in 4 autologous stem cell transplantation, in 2 allogeneic stem cell transplantation, for 4 patients data were missing. Detailed description of patients' characteristics is reported in table 1. Twenty-six patients were treated with Bamlaniimab/Eteseimab, 17 with Casiriimab/Imdeimab, 3 with Bamlaniimab, and 2 with Sotroimab, for 3 patients data were missing. Median time to SARS-CoV-2 molecular swab negatiization was ealuable in 41 subjects and was 17 days (min 5, IQR 12-26, max 174). This result compared well with the preious finding of 28 days reported in an historical group of HM patients not treated with nMoAbs. We did not find any subpopulation, according to age, diagnosis, period of infection or type of nMoAbs who achieed a major benefit from nMoAbs treatment. The rate of Hospitalization due to COVID-19 progression was 19% (10/51), with an extremely low percentage of patients requiring ICU admission due to seer COVID-19 (2%,1/51). Most frequent side effects included chills (8%), diarrhea (6%), headache (2%), nausea (2%) and omiting (2%). Summary/Conclusion: Among paucisymptomatic SARS-CoV-2 positie HM patients on actie treatment or in disease remission within 6 months from treatment discontinuation, the administration of nMoAbs substantially reduced the time to swab negatiization compared to an historical control of HM subjects. This treatment was also able to reduce the rate of Hospitalization and death due to COVID-19 progression in this high risk group. (Table Presented).

Managing hematological cancer patients during the COVID-19 pandemic: an ESMO-EHA Interdisciplinary Expert Consensus.

BACKGROUND: The COVID-19 pandemic has created enormous challenges for the clinical management of patients with hematological malignancies (HMs), raising questions about the optimal care of this patient group. METHODS: This consensus manuscript aims at discussing clinical evidence and providing expert advice on statements related to the management of HMs in the COVID-19 pandemic. For this purpose, an international consortium was established including a steering committee, which prepared six working packages addressing significant clinical questions from the COVID-19 diagnosis, treatment, and mitigation strategies to specific HMs management in the pandemic. During a virtual consensus meeting, including global experts and lead by the European Society for Medical Oncology and the European Hematology Association, statements were discussed and voted upon. When a consensus could not be reached, the panel revised statements to develop consensual clinical guidance. RESULTS AND CONCLUSION: The expert panel agreed on 33 statements, reflecting a consensus, which will guide clinical decision making for patients with hematological neoplasms during the COVID-19 pandemic.

COVID-19 Infection in Vaccinated Adult Patients with Hematological Malignancies. Preliminary Results from Epicovideha (Epidemiology of COVID-19 infection in patients with hematological malignancies: A European Haematology Association Survey)

Introduction Coronavirus disease 2019 (COVID-19) is a life-threatening condition of high relevance for co-morbid patients, such as those with baseline hematological malignancies (HM). One year after the diagnosis of the first COVID-19 case, at the end of 2020, the first vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were administered to the population, starting with individuals at highest risk of infection. EPICOVIDEHA aims to describe the epidemiology, vaccination strategies and mortality rates from HM patients at risk. Methods We collected clinical and epidemiological data from patients with laboratory-based diagnosis of SARS-CoV-2 infection after partial or complete vaccination. The study was sponsored by the European Hematology Association - Infectious Diseases Working Party. Patients were registered in the EPICOVIDEHA online survey between January 1, 2021 and July 31, 2021 from Europe and United States. Data captured included underlying conditions prior to SARS-CoV-2, HM status and management prior to SARS-CoV-2, SARS-CoV-2 vaccination and infection details and mortality. The survey will continue until December 31, 2021. Results Overall, 40 patients have been so far registered, 24 male and 16 females, the vast majority of them aged over 50 years (N=38, 95%). Three quarters of patients were affected by lymphoproliferative malignancies (chronic lymphoid leukemia [CLL] N=14 and non-Hodgkin lymphoma [NHL] and multiple myeloma [MM] N=8, each), followed by myelodysplastic syndrome (MDS) (N=4), acute myeloid leukemia (AML) (N=2) and others (chronic myeloid leukemia [CML], acute lymphoid leukemia [ALL], polycythemia vera [PV] and aggressive mastocytosis one of each). Thirty-one patients (77.5%) were receiving active treatment for underlying HM at the time of SARS-CoV-2 infection, with 16 of them being on chemotherapy in the month prior to infection. All patients were vaccinated with a median time from vaccine to SARS-CoV-2 infection of 45.5 days (IRQ 19-67.5). Twenty-nine patients received a mRNA vaccine (BioNTech/Pfizer N=28, Moderna COVE N=1), whereas the remaining 11 an inactivated vaccine (Sinovac CoronaVac N=6) and vector-based vaccine (AstraZeneca Oxford N=5). Twenty-three patients were completely vaccinated, of which 22 (97.5%) patients were immunized (a minimum of 15 days following second dose). On the contrary, among 17 patients partially vaccinated, none was immunized. In 9 cases, viral genomes were analyzed (English variant N=7, South Africa variant N=1, Indian variant N=1). Overall, 25/40 patients presented with a severe/critical infection (62.5%), 13 of which (52%) were fully vaccinated and immunized, whereas only 15 (37.5%) were asymptomatic or mildly symptomatic. Twenty-seven (92.5%) patients were admitted to hospital, 5/27 (18.5%) to ICU, all requiring mechanical ventilation. After a follow-up of 30 day from SARS-CoV-2 infection, 8 patients died (20%), with 7/8 deaths (87.5%) attributable to SARS-CoV-2. There was no difference in overall survival between those patients that received 2 doses of vaccine or 1 dose (figure 1a), as well as no difference being observed between patients with and without lymphoproliferative malignancies (figure 1b), patients that receiving/not receiving active treatment in the last month (figure 1c), or the type of vaccine injected (figure 1d). Conclusions Our survey, involving over 150 Hematology Departments around the world, provides some preliminary insights. The majority of patients who do not respond to vaccination are patients with lymphoproliferative diseases, as can also be observed for other types of vaccination (e.g., flu-vaccination). Dramatically the mortality observed in all patients, although lower than that observed in the pre-vaccination period which in our experience was around 31%, still remains high (20%). Recruitment to this survey continues, and we hope that with larger numbers of cases, more definitive conclusions can be drawn to develop strategies to keep these complex patients safe. [Formula presented] Disclosures: Lop z-Garcia: Celgene: Other: Speaker Honoraria;Abbvie: Other: Speaker Honoraria, Advisor, Travel and accommodation grants;Janssen: Other: Speaker Honoraria, Advisor, Travel and accommodation grants, Research Funding;Roche: Other: Speaker Honoraria, Travel and accommodation grants;Novonordisk: Other: Speaker Honoraria;Fresenius: Other: Speaker Honoraria. Glenthoej: Novo Nordisk: Honoraria;Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees;bluebird bio: Consultancy, Membership on an entity's Board of Directors or advisory committees;Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees;Alexion: Research Funding. Mikulska: Biotest: Speakers Bureau;Janssen: Speakers Bureau;MSD: Speakers Bureau;Gilead: Speakers Bureau;Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Busca: Gilead Sciences: Other: Lecture Honoraria;Merck: Other: Lecture Honoraria;Pfizer Pharmaceuticals: Other: Lecture Honoraria;Basilea: Other: Lecture Honoraria;Biotest: Other: Lecture Honoraria;Jazz Pharmaceuticals: Other: Lecture Honoraria;Takeda: Membership on an entity's Board of Directors or advisory committees. Corradini: KiowaKirin;Incyte;Daiichi Sankyo;Janssen;F. Hoffman-La Roche;Kite;Servier: Consultancy;AbbVie, ADC Theraputics, Amgen, Celgene, Daiichi Sankyo, Gilead/Kite, GSK, Incyte, Janssen, KyowaKirin, Nerviano Medical Science, Novartis, Roche, Sanofi, Takeda: Honoraria;AbbVie, ADC Theraputics, Amgen, Celgene, Daiichi Sankyo, Gilead/Kite, GSK, Incyte, Janssen, KyowaKirin, Nerviano Medical Science, Novartis, Roche, Sanofi, Takeda: Consultancy;Amgen;Takeda;AbbVie: Consultancy, Honoraria, Other: Travel and accommodations;Novartis;Gilead;Celgene: Consultancy, Other: Travel and accommodations;BMS: Other: Travel and accommodation;Sanofi: Consultancy, Honoraria;Incyte: Consultancy;Novartis, Janssen, Celgene, BMS, Takeda, Gilead/Kite, Amgen, AbbVie: Other: travel and accomodations. Hoenigl: Gilead, Pfizer, Astellas, Scynexis, and NIH: Research Funding. Klimko: Gilead Science, MSD, Pfizer: Membership on an entity's Board of Directors or advisory committees;Gilead Sciences, MSD, Pfizer Pharmaceuticals, and Astellas Pharma: Speakers Bureau. Pagliuca: Gentium/Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Gilead, Pfizer, and MSD: Research Funding. Passamonti: Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;AbbVie: Speakers Bureau;BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Köhler: German Federal Ministry of Research and Education and the State of North Rhine-Westphalia, Germany: Other: Support;Miltenyi Biotec GmbH, Bergisch Gladbach, Germany, and the Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany: Other: Non-financial grants;Akademie für Infektionsmedizin e.V., Ambu GmbH, Astellas Pharma, European Confederation of Medical Mycology, Gilead Sciences, GPR Academy Ruesselsheim, MSD Sharp & Dohme GmbH, Noxxon N.V., and University Hospital, LMU Munich: Consultancy, Honoraria. Cornely: Amplyx, Basilea, BMBF, Cidara, DZIF, EU-DG RTD (101037867), F2G, Gilead, Matinas, MedPace, MSD, Mundipharma, Octapharma, Pfizer, Scynexis: Other: Grants or Contracts. Pagano: Gilead Science, MSD, Pfizer, Basilea, Janssen, Novartis, Jazz Pharmaceutical, Cidara: Membership on an entity's Board of Directors or advisory committees;Gilead Sciences, MSD, Pfizer Pharmaceuticals, Astellas Pharma: Speakers Bureau;Menarini: Consultancy.