-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

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Ticketed Session denotes that this is a ticketed session.

315 Second Versus First Wave of COVID-19 in Patients with MPNClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Transplantation, COVID-19 and Biology Insights
Hematology Disease Topics & Pathways:
Epidemiology, Non-Biological, Clinical Research, Clinically Relevant, Diseases, SARS-CoV-2/COVID-19, Infectious Diseases, Therapies, Myeloid Malignancies, Pharmacology
Saturday, December 11, 2021: 4:30 PM

Tiziano Barbui1*, Alessandra Iurlo, MD, PhD2*, Arianna Masciulli, PhD3*, Alessandra Carobbio, BSc3*, Arianna Ghirardi, BSc3*, Greta Carioli, PhD3*, Marta Sobas4*, Elena Maria Elli, MD5*, Elisa Rumi, MD6*, Valerio De Stefano7*, Francesca Lunghi, MD8*, Monia Marchetti9*, Rosa Daffini, MD10*, Mercedes Gasior Kabat, MD11*, Beatriz Cuevas, MD12*, Laura Maria Fox, MD13*, Marcio Andrade, MD, PhD14*, Francesca Palandri, MD, PhD15*, Paola Guglielmelli, MD, PhD16, Giulia Benevolo, MD17*, Claire N. Harrison, DM18, Maria Angeles Foncillas, MD19*, Massimiliano Bonifacio, MD20*, Alberto Alvarez-Larran21*, Jean-Jacques Kiladjian, MD, PhD22, Estefanía Bolaños, MD23*, Andrea Patriarca, MD24*, Keina Quiroz, MD25*, Martin Griesshammer, MD, PhD26*, Valentín Garcia Gutierrez, MD, PhD27, Alberto Marin Sanchez, MD28*, Elena Magro, MD29*, Marco Ruggeri, MD30, Juan Carlos Hernandez Boluda, MD31*, Santiago Osorio, MD32*, Gonzalo Carreño Gomez-Tarragona, MD33*, Miguel Sagüés, MD34*, Rajko Kusec, MD, PhD35*, Begoña Navas, MD36*, Anna Angona, MD37*, Blanca Xicoy, MD38*, Emma Lopez Abadia, MD39*, Steffen Koschmieder, MD40, Daniele Cattaneo, MD2,41*, Cristina Bucelli, MD2*, Edyta Cichocka, MD PhD42*, Anna Masternak, MD43*, Fabrizio Cavalca, MD5*, Oscar Borsani, MD6*, Silvia Betti, MD, PhD7*, Marta Bellini, MD44*, Natalia Curto-Garcia, MD18*, Alessandro Rambaldi, MD41,44 and Alessandro Vannucchi, MD45

1FROM Research Foundation ASST Papa Giovanni XXIII Bergamo, Bergamo, Italy
2Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
3FROM Research Foundation Ospedale di Bergamo, Bergamo, Italy
4Department of Hematology, Blood Neoplasm and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland
5Hematology Division and Bone Marrow Transplant Unit, San Gerardo Hospital, ASST Monza, Monza, Italy
6Department of Molecular Medicine, University of Pavia, Pavia, Italy
7Section of Hematology, Catholic University, Fondazione Policlinico "A. Gemelli" IRCCS, Rome, Italy
8Hematology and Bone Marrow Transplantation Unit, IRCCS Ospedale San Raffaele, Milano, Italy
9Hematology Unit, Az Osp SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy
10Hematology, ASST Spedali Civili di Brescia, Brescia, Italy
11Hospital Universitario La Paz, Madrid, ESP
12Hematology, Hospital Universitario de Burgos, BURGOS, ESP
13Department of hematology, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Hospital Universitari, Barcelona, Spain
14Hematology Department, Hospital del Mar, Barcelona, Spain
15IRCCS Azienda Ospedaliero-Universitaria S. Orsola-Malpighi, Bologna, Italy
16CRIMM, Center Research and Innovation of Myeloproliferative Neoplasms, University of Florence, AOU Careggi, Florence, Italy
17Hematology Division , Città della Salute e della Scienza Hospital, TORINO, TO, Italy
18Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
19Hospital Universitario Infanta Leonor, Madrid, Spain
20Ospedale Policlinico “G.B. Rossi”, Borgo Roma, Verona, Italy
21Hematology Department, Hematology Department, Hospital ClíNic, Barcelona, Spain
22Hôpital Saint-Louis; Université de Paris, INSERM, Paris, France
23Hospital Clinico San Carlos, Madrid, Spain
24AOU Maggiore della Carità, Novara, Novara, Italy
25Hospital Universitario de Móstoles, Madrid, Spain
26University Clinic for Hematology, Oncology, Haemostaseology and Palliative Care, Johannes Wesling Medical Center, Minden, University of Bochum, Minden, Germany
27Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain
28Hospital General Universitario De Albacete, Albacete, ESP
29Hospital Universitario Principe de Asturias, Alcalá de Henares, Spain
30Hematology Department, San Bortolo Hospital, Azienda ULSS8 "Berica" di Vicenza, Vicenza, Italy
31Department of Hematology, Hospital Clínico Universitario de Valencia, Instituto de Investigación Sanitaria INCLIVA, VALENCIA, Spain
32Hospital General U. Gregorio Marañón, Madrid, Spain
33Hematology Department, Hospital Universitario 12 de Octubre,, Madrid, Spain
34ICO L’Hospitalet-Hospital Moises Broggi, Sant Joan Despì, Spain
35Department of haematology, Clinic of internal medicine, University Hospital Dubrava-School of Medicine University of Zagreb, Zagreb, Croatia
36Hematology and hemotherapy department, Hospital Universitario HLA Moncloa, Madrid, Spain
37Institut Català d'Oncologia - Girona Hospital Josep Trueta, Girona, Spain
38Institut Català d'Oncologia-Hospital Germans Trias i Pujol, Badalona, Spain
39Hospital General De Elche, Elche, Alicante, Spain
40Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen, Germany
41University of Milan, Milan, Italy
42Department of Hematology and Bone Marrow Transplantation, Copernicus Memorial Hospital, Torun, Poland
43Department of Hematology and Internal Diseases, State Hospital, Opole, Poland
44Hematology and Bone Marrow Transplant Unit, ASST Papa Giovanni XXIII, Bergamo, Italy
45University of Florence, Firenze, Italy

Introduction. MPN-COVID is a European LeukemiaNet cohort study, launched in March 2020 in patients with myeloproliferative neoplasms (MPN) with COVID-19. The first cohort of 175 cases was analyzed at the end of first wave (July 2020) and results provided estimates and risk factors of overall mortality (Barbui T. Leukemia, 2021), thrombosis incidence (Barbui T. Blood Cancer J, 2021), and post-COVID outcomes (Barbui T. Blood Cancer J, 2021). In the second wave of pandemic (June 2020 to June 2021), case-fatality risk in the general population has been found variable across different countries, and no information is available in MPN patients with COVID-19 diagnosed during the second wave in comparison with those of the first wave.

Methods. In an electronic case report form, we registered a total of 479 cases of ET (n=161, 34%), PV (n=135, 28%), pre-PMF (n=49, 10%) and overt MF (n=134, 28%), from 39 European hematology units (Italy, Spain, Germany, France, UK, Poland, Croatia). Of these, 304 were diagnosed COVID-19 during the second wave.

Results.

  • Patients in the second wave were significantly different from those in the first wave, including parameters such as age (median: 63 vs. 71 years, p<.001), sex (females: 52% vs. 42%, p=0.037), MPN category (MF 24% vs. 34%, p=0.020), comorbidity (at least one comorbidity 63% vs. 74%, p=0.012), disposition (home: 68% vs. 23%, regular ward: 29% vs. 66%, ICU: 3% vs. 11%, p<.001), need of respiratory support (28% vs. 59%, p<.001) and degree of systemic inflammation (C-Reactive Protein: 51% vs. 74%, p=0.008; Neutrophil to Lymphocyte Ratio: 4.1 vs. 5.4, p=0.038).
  • In regard to COVID-19-directed therapy, in the second wave steroids were more frequently prescribed (28% vs. 40%, p=0.007), while the use of antibiotics, antivirals, hydroxychloroquine and experimental therapies was significantly less frequent (p<.001 for all the differences). Interestingly, only 4 out of 46 patients (8.7%) discontinued Ruxolitinib during second-wave acute COVID (all MF admitted to regular ward).
  • In the two waves, distribution probability of COVID-19 incidence by Kernel method showed a substantially similar shape, whereas the two incidence peaks were associated with very different mortality, as reported in Fig. 1A. The difference between the probability of death was highly significant during the first (n=175) vs. second (n=304): 31% vs. 9% at 60 days from COVID-19 diagnosis, respectively (p<.001) (Fig. 1B). Of note, among 26 deaths, 4 (15%) occurred at home, 19 (73%) on regular wards and 3 (12%) in the ICU, and death more frequently afflicted patients with (n=17, 65%) than ET (n=5, 19%) and PV (n=4. 15%) (p<.001).
  • Independent risk factors for death in a multivariate Cox regression model fitted on the whole cohort and adjusted for the wave to which patients belonged, were age over 70 years (HR=5.2, 95% CI 1.8-15.1, p=0.002), male sex (HR=1.9, 95% CI 1.1-3.1, p=0.016), COVID-19 severity revealed by the need for respiratory support (HR=4.5, 95% CI 1.9-10.7, p=0.001), and Ruxolitinib discontinuation (HR=3.0, 95% CI 1.3-6.9, p=0.011). Conversely, in patients who continued this drug, no risk was documented (HR=1.21, p=0.566).
  • Taking into account death as competing event, the second outcome of interest was the incidence of thrombosis, wich occurred in a significantly lower proportion of patients in the second wave compared to the first one (n=5 [1.6%] vs. n=14 [8.0%] at +60 days, respectively, SHR=0.20, p=0.002) (Fig. 1C). All the events, but one (n=4/5) were venous and were reported in patients with ET (SHR=4.4, 95% CI 1.8-10.7, p=0.001).

Conclusions. This is the largest series of MPN patients who incurred COVID-19 from June 2020 onward, namely during the “second COVID-19 wave”. Compared to the first wave, the second one recorded a lower overall COVID-19 severity, but Ruxolitinib discontinuation still remained a risk factor for a dismal outcome. Greater vulnerability of ET than PV in developing venous thrombosis was confirmed also during the second wave. This finding suggests that ET warrants a specific antithrombotic prophylaxis in addition to heparin.

Disclosures: Barbui: AOP Orphan: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Iurlo: Novartis: Speakers Bureau; Incyte: Speakers Bureau; Pfizer: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Sobas: Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Fox: Novartis: Honoraria; Sierra: Honoraria. Palandri: AOP: Membership on an entity's Board of Directors or advisory committees; CTI: Consultancy; Sierra Oncology: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Benevolo: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau. Harrison: Gilead Sciences: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sierra Oncology: Honoraria; Galacteo: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Promedior: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CTI BioPharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte Corporation: Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Keros: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: 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, Research Funding, Speakers Bureau; Geron: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AOP Orphan Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Constellation Pharmaceuticals: Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Bonifacio: Pfizer: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Kiladjian: Taiho Oncology, Inc.: Research Funding; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Incyte Corporation: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; PharmaEssentia: Other: Personal fees; AOP Orphan: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees. Patriarca: Incyte: Honoraria; Takeda: Honoraria; Argenix: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Pfizer: Honoraria. Griesshammer: Janssen: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Shire: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; AOP Orphan: Consultancy, Honoraria; CTI: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria. Garcia Gutierrez: Pfizer: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Osorio: Janssen, Abbvie, Roche: Consultancy. Koschmieder: CTI: Membership on an entity's Board of Directors or advisory committees, Other; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Baxalta: Membership on an entity's Board of Directors or advisory committees, Other; Abbvie: Other: Travel support; Alexion: Other: Travel support; Karthos: Other: Travel support; Sanofi: Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Image Biosciences: Other: Travel support; AOP Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding; Geron: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Shire: Honoraria, Other. Vannucchi: Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH