-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.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

3033 Protection Against Breakthrough Delta/Omicron Variants in Vaccinated Patients with Myeloproliferative Neoplasms (MPN)

Program: Oral and Poster Abstracts
Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, epidemiology, MPN, Clinical Research, Chronic Myeloid Malignancies, Diseases, registries, Myeloid Malignancies
Sunday, December 11, 2022, 6:00 PM-8:00 PM

Tiziano Barbui, MD1*, Alessandra Carobbio, MSc1*, Arianna Ghirardi, PhD1*, Alessandra Iurlo, MD, PhD2*, Valerio De Stefano, MD3*, Marta Anna Sobas, MD, PhD4*, Elisa Rumi, MD5*, Elena Maria Elli, MD6*, Francesca Lunghi, MD7*, Mercedes Gasior Kabat, MD8*, Beatriz Cuevas, MD9*, Paola Guglielmelli, MD, PhD10, Massimiliano Bonifacio, MD11*, Monia Marchetti12*, Alberto Alvarez-Larran, MD, PhD13*, Laura Maria Fox, MD14*, Marta Bellini, MD15*, Rosa Daffini, MD16*, Giulia Benevolo, MD17*, Gonzalo Carreño, MD PhD18*, Andrea Patriarca, MD19*, Haifa Kathrin Al-Ali, MD20*, Marcio Andrade, MD, PhD21*, Francesca Palandri, PhD, MD22*, Claire N. Harrison, DM23, Maria Angeles Foncillas, MD24*, Santiago Osorio, MD25*, Steffen Koschmieder26, Elena Magro, MD27*, Jean-Jacques Kiladjian, MD28, Estefanía Bolaños, MD29*, Florian H. Heidel, MD30, Keina Quiroz, MD31*, Martin Griesshammer32*, Valentín García Gutiérrez, PhD33, Alberto Marin Sanchez, MD34*, Juan Carlos Hernandez Boluda, MD, PhD35*, Emma Lopez Abadia, MD36*, Giuseppe Carli, MD37*, Miguel Sagüés, MD38*, Rajko Kusec, MD, PhD39*, Blanca Xicoy, MD40*, Margarita Guenova, PhD41*, Begoña Navas, MD42*, Anna Angona, MD43*, Edyta Cichocka, MD44*, Anna Masternak, MD45*, Daniele Cattaneo, MD2,46*, Cristina Bucelli, MD47*, Silvia Betti, MD, PhD3*, Oscar Borsani, MD5, Fabrizio Cavalca48*, Sara Carbonell, MD13*, Natalia Curto-Garcia, MD23*, Lina Benajiba, MD, PhD49*, Alessandro Rambaldi, MD15,46 and Alessandro M. Vannucchi10

1FROM Research Foundation Ospedale di Bergamo, Bergamo, Italy
2Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
3Section of Hematology, Catholic University, Fondazione Policlinico "A. Gemelli" IRCCS, Rome, Italy
4Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland
5Department of Molecular Medicine, University of Pavia, Pavia, Italy
6San Gerardo Hospital, ASST Monza, Monza, Italy
7Department of Onco-Haematology - Haematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute and Vita-Salute Hospital, Milano, Italy
8Hospital Universitario La Paz, Madrid, ESP
9Hematology, Hospital Universitario de Burgos, BURGOS, ESP
10CRIMM, Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
11Department of Medicine, Section of Hematology, University of Verona and Azienda Ospedaliera Universitaria Integrata, Verona, Italy
12Division of Hematology, Hospital Antonio e Biagio and Cesare Arrigo, Alessandria, Italy
13Hematology Department, Hospital Clínic, Barcelona, Spain
14Department of hematology, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Hospital Universitari, Barcelona, Spain
15Department of Oncology-Hematology, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy
16Department of Hematology, ASST Spedali Civili, Brescia, Italy
17Division of Hematology, AOU "Città della Salute e della Scienza di Torino", Turin, Italy
18Hematology Department, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Imas12, Madrid, Spain
19Hematology Unit, Department of Translational Medicine, University of Eastern Piedmont and AOU Maggiore della Carità, Novara, Italy
20Krukenberg Cancer Center Halle, University Hospital Halle (Saale), Halle/ Saale, Germany
21Hematology Department, Hospital del Mar, Barcelona, Spain
22IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli", Bologna, Italy
23Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom
24Hospital Universitario Infanta Leonor, Madrid, Spain
25Hospital General U. Gregorio Marañón, Madrid, Spain
26Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Faculty of Medicine, University Hospital of Aachen, Aachen, Germany
27Hospital Universitario Principe de Asturias, Alcalá de Henares, Spain
28Hopital Saint-Louis, Paris, France
29Hospital Clinico San Carlos, Madrid, Spain
30Innere Medicin C, Universitätsmedizin Greifswald, Greifswald, Germany
31Hospital Universitario de Móstoles, Madrid, Spain
32University Clinic for Hematology, Oncology, Haemostaseology and Palliative Care, Johannes Wesling Medical Center, Minden, University of Bochum, Minden, Germany
33Hematology Service, Hospital Universitario Ramón y Cajal. IRYCIS, Madrid, Spain
34Hospital General Universitario De Albacete, Albacete, ESP
35Department of Hematology, Hospital Clínico Universitario de Valencia, Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain
36Hospital General De Elche, Elche, Alicante, Spain
37Department of Hematology, S. Bortolo Hospital, Vicenza, Vicenza, Italy
38Hospital de Sant Joan Despí Moisès Broggi, Sant Joan Despí, Barcelona, Spain
39Department of haematology, Clinic of internal medicine, University Hospital Dubrava-School of Medicine University of Zagreb, Zagreb, Croatia
40HU German Trias i Pujol - Institut Català d' Oncologia, Barcelona, Spain
41Laboratory of Hematopathology & Immunology, National Specialised Hospital for Active Treatment of Hematological Diseases, Sofia, BGR
42Hematology and hemotherapy department, Hospital Universitario HLA Moncloa, Madrid, Spain
43HU Dr. J Trueta - Institut Català d'Oncologia, Girona, Spain
44Department of Hematology and Bone Marrow Transplantation, Copernicus Memorial Hospital, Torun, Poland
45Department of Hematology and Hematooncology, District Specialist Hospital, Opole, Opole, Poland
46University of Milan, Milan, Italy
47Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
48Hematology Division and Bone Marrow Transplant Unit, San Gerardo Hospital, ASST Monza, Monza, Italy
49Hôpital Saint-Louis, Université de Paris, Paris, France

Background Information on breakthrough SARS-CoV-2 infections in MPN vaccinated patients (pts) is very limited. In these diseases, effectiveness of coronavirus disease 2019 (Covid-19) vaccines may be influenced not only by the MPN phenotype and the intrinsic reduced immunological competence, but also by the prior Covid-19 infection that can elicit a natural immunity against reinfections.

Patients In the European LeukemiaNet (ELN) observational registry, 863 MPN pts with Covid-19 have been enrolled since February 2020 and in 649 of them, information on the vaccination status is now available. To ensure that well characterized reinfections were considered, diagnosis of breakthrough Covid-19 included a positive naso-pharyngeal swab and symptoms highly suggestive for SARS CoV-2 infection.

Results

  • Breakthrough infections in vaccinated patients with previous Covid-19 infection

The effectiveness of previous Covid-19 infection in preventing reinfections was tested in a group of 131 and 287 unvaccinated and vaccinated MPN pts, respectively. Prior Covid-19 occurred during the first and second wave in 74% and 98% pts, respectively and the interval between Covid-19 and the breakthrough infection in unvaccinated and in vaccinated was similar (8.5 months). Administered vaccine doses (Pfizer in 71%) were 1-2 and 3-4 in 77% and 23% of vaccinated cases, respectively. The proportion of PV, ET, pre-PMF was similar in the two groups while the number of MF pts was lower (19%) than in the unvaccinated group (28%) (p=0.024). Reinfections occurred during delta (n=4) or omicron variants period (n=14) in 8 (6.1%) and 10 (3.5%) unvaccinated and vaccinated pts (p=ns) and hospitalization was required in 0 and 2 pts, respectively. Severity of the acute infection was variable and 1 death was registered.

  • Breakthrough infections in vaccinated patients without previous Covid-19 infection

Breakthrough infections were reported in 231 vaccinated cases (ET=89, PV=75, MF=54 and pre-PMF=13) without prior Covid-19. In 51% of pts the administered vaccine doses were 1-2 and 3-4 in 49%. No relevant vaccine related side effects were registered. Time interval from vaccination to Covid-19 was 8.1 months. Twenty-six pts (11%) required hospitalization and 205 (89%) were managed at home. Hospitalized pts were older (median age 76), males (69%) with MF (39%), and prior exposure to ruxolitinib (42%, 7 MF and 4 PV). Of note, values of C-reactive protein (CRP) and neutrophil/lymphocyte ratio (NLR) were significantly more elevated in hospitalized cases (CRP=33.1 vs. 2.0 and NLR=5.9 vs. 3.3, p<0.001). Although some infections occurred in the second wave, corresponding to alpha/beta/gamma coronavirus infection (6%), the majority of breakthrough episodes occurred in delta and omicron variant periods (41% and 53%). Three deaths were registered in hospitalized pts. We explored the risk of hospitalization and evaluated the marginal effect of gender, age and ruxolitinib exposure in a logistic model fitted to predict this event. We found that the risk of hospitalization was substantially higher only in males on ruxolitinib and increased with age (Figure). We also found that the inflammatory status measured with NLR could explain these results (data not shown).

Conclusion The effectiveness of previous Covid-19 in preventing reinfection occurring during the delta and omicron variants of SARS-CoV-2 was robust (94% and 97% in unvaccinated and vaccinated pts, respectively). This is good news for MPN patients who recovered from Covid-19 and the hope is that this effectiveness can work against any future SARS-CoV-2 variant. In the cohort of vaccinated pts without prior Covid-19, we identified a subgroup of patients with more severe delta and omicron disease, at high risk of hospitalization, consisting of males who were on ruxolitinib and had elevated inflammatory biomarkers. Subsequent studies are needed to interpret these latest results.

Disclosures: Barbui: AOP Orphan Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Carobbio: Novartis: Speakers Bureau. Iurlo: Novartis, BMS, Celgene, Incyte, Pfizer: Honoraria. De Stefano: AbbVie: Honoraria; GlaxoSmithKline: Honoraria, Speakers Bureau; Bristol Myers Squibb/Celgene: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; 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. Sobas: Novartis: Honoraria; Celgene/BMS: Honoraria. Gasior Kabat: Eusa Pharma: Speakers Bureau; Novartis: Other: Advisory Board , Speakers Bureau; Brystol Myers Squibb: Other: Advisory Board . Guglielmelli: Novartis, Abbvie: Other: Other member of advisory board, speaker at meeting. Benevolo: Bristol Myers Squibb: 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, Speakers Bureau. Patriarca: Incyte: Honoraria, Speakers Bureau; Sanofi: Honoraria; Novartis: Honoraria, Speakers Bureau. Al-Ali: Abbvie: Consultancy; Deutsche Leukämie und Lymphom Stiftung: Other: Grants and Contracts; BMS: Other: Grants and Contracts; Incyte: Other: Grants and Contracts; Novartis: Consultancy, Honoraria, Other: Support for attending meetings and/or travel and Participation on a Data Safety Monitoring Board or Advisory Board; AOP: Consultancy, Other: Support for attending meetings and/or travel. Palandri: Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Sierra Oncology: Consultancy, Honoraria; CTI: Consultancy, Honoraria; Sobi: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Kartos/Telios: Consultancy, Honoraria; AOP: Consultancy, Honoraria. Harrison: Geron: Membership on an entity's Board of Directors or advisory committees; Keros: Consultancy; Constellation Pharmaceuticals, Inc., a MorphoSys Company: Membership on an entity's Board of Directors or advisory committees, Research Funding; EHA: Other: Leadership role; MPN voice: Other: Leadership role; AbbVie: Membership on an entity's Board of Directors or advisory committees; Incyte: Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees; Sierra: Honoraria; AOP Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Promedior: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; CTI BioPharma: Membership on an entity's Board of Directors or advisory committees; Galecto: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings, Research Funding; Galacteo: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding. Osorio: Janssen, Abbvie, Roche: Consultancy. Koschmieder: Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Ariad: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; CTI Biopharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; PharmaEssentia: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Alexion: Other: Travel support; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Imago Biosciences: Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Karthos: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Sierra Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; RWTH Aachen University: Patents & Royalties: BET Inhibitor; AOP Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Geron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding. Kiladjian: 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; Incyte: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Heidel: AOP: Consultancy; CTI: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. García Gutiérrez: Roche: Research Funding; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Incyte: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Kusec: Abbvie: Consultancy, Speakers Bureau. Guenova: Merck: Consultancy; Pfizer: Consultancy; Novartis: Other: Lectures; Roche: Other: Lectures; Astra Zeneka: Other: Lectures. Benajiba: Gilead: Research Funding; Pfizer: Research Funding. Rambaldi: Roche: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Kite-Gilead: Honoraria; Jazz: Honoraria; ABBVIE: Honoraria; Astellas: Honoraria; Pfizer: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Celgene-BMS: Honoraria; Omeros: Honoraria. Vannucchi: Abbvie: Membership on an entity's Board of Directors or advisory committees; AOP Orphans Pharmaceuticals: 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; Morphosys: Membership on an entity's Board of Directors or advisory committees; BluePrint: Membership on an entity's Board of Directors or advisory committees, Other: NA; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees, Other: NA; 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, Speakers Bureau.

*signifies non-member of ASH