Breakthrough COVID-19 in vaccinated patients with hematologic malignancies: results from EPICOVIDEHA survey

Livio Pagano (1) , Jon Salmanton-García (2) , Francesco Marchesi (1) , Ola Blennow (3) , Maria Gomes da Silva (4) , Andreas Glenthøj (5) , Jaap van Doesum (6) , Yavuz Bilgin (6) , Alberto Lopez-Garcia (7) , Federico Itri (8) , Raquel Nunes Rodrigues (4) , Barbora Weinbergerová (9) , Francesca Farina (8) , Giulia Dragonetti (10) , Caroline Berg Venemyr (5) , Jens van Praet (11) , Ozren Jaksic (12) , Toni Valkovic (13) , Iker Falces-Romero (14) , Sonia Martin-Perez (15) , Moraima Jiménez (16) , Julio Davila-Valls (15) , Martin Schonlein (17) , Emanuele Ammatuna (16) , Stef Meers (18) , Mario Delia (19) , Zlate Stojanoski (20) , Anna Nordlander (3) , Tobias Lahmer (21) , László Imre Pinczés (22) , Caterina Buquicchio (23) , Klára Piukovics (24) , Irati Ormazabal-Velez (25) , Nicola Stefano Fracchiolla (26) , Michail Samarkos (27) , Gustavo-Adolfo Mendez (28) , José-Ángel Hernández-Rivas (29) , Ildefonso Espigado (30) , Martin Cernan (31) , Verena Petzer (32) , Sylvain Lamure (33, 34) , Roberta Di Blasi (35) , Joyce Marques de Almeida (36) , Michelina Dargenio (37) , Monika Maria Biernat (36) , Mariarita Sciumè (38) , Cristina de Ramón (39) , Nick Alexander de Jonge (40) , Josip Batinic (12) , Avinash Aujayeb (41) , Monia Marchetti (42) , Guillemette Fouquet (43) , Noemi Fernández Escalada (44) , Giovanni Paolo Maria Zambrotta (45) , Maria Vittoria Sacchi (42) , Anna Guidetti (46) , Fatih Demirken (47) , Lucia Prezioso (48) , Zdenek Racil (49) , Marcio Nucci (50) , Miloš Mladenovic (51) , Raphaël Lievin (35) , Michaela Hanakova (49) , Stefanie Grafe (17) , Uluhan Sili (52) , Marina Machado (29) , Chiara Cattaneo (53) , Tatjana Adzic-Vukicevic (51) , Luisa Verga (45) , Jorge Labrador (54) , Laman Rahimli (2) , Matteo Bonanni (55) , Francesco Passamonti (56) , Antonio Pagliuca (57) , Paolo Corradini (58) , Martin Hoenigl (59) , Philipp Koehler (60) , Alessandro Busca (61) , Oliver Cornely (2)

1 Unicatt - Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma]
2 University Hospital of Cologne [Cologne]
3 Karolinska University Hospital [Stockholm]
4 IPO Porto - Instituto Português de Oncologia do Porto / Portuguese Oncology Institute of Porto
5 Copenhagen University Hospital
6 UMCG - University Medical Center Groningen [Groningen]
7 Hospital Universitario HM Sanchinarro [Madrid, Spain]
8 IRCCS Ospedale San Raffaele [Milan, Italy]
9 University Hospital Brno
10 Fondazione Policlinico Universitario Agostino Gemelli IRCCS
11 Openbare Bibliotheek Brugge
12 University of Zagreb
13 University of Rijeka
14 La Paz University Hospital
15 UNICA - Universidad de Ciego de Avila
16 UAB - Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona
17 UKE - Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg]
18 VIB [Belgium]
19 Polytechnic University of Bari / Politecnico di Bari
20 Institute of Public Health of Republic of North Macedonia [Skopje]
21 University-Hospital Munich-Großhadern [München]
22 University of Debrecen Egyetem [Debrecen]
23 ICB - Istituto di chimica biomolecolare [Padova, Italy]
24 University of Szeged [Szeged]
25 UNAV - Universidad de Navarra [Pamplona]
26 Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan]
27 University of Athens Medical School [Athens]
28 UCA - Pontificia Universidad Católica Argentina
29 Hospital General Universitario "Gregorio Marañón" [Madrid]
30 Universidad de Sevilla = University of Seville
31 Univerzita Palackého [Olomouci]
32 IMU - Innsbruck Medical University = Medizinische Universität Innsbruck
33 CHU Montpellier
34 IGMM - Institut de Génétique Moléculaire de Montpellier
35 AP-HP - Hopital Saint-Louis [AP-HP]
36 Wrocław Medical University
37 University of Salento [Lecce]
38 Unit of Melanoma Medical Oncology [Fondazione IRCCS Istituto Nazionale Tumori, Milan]
39 Universidad de Salamanca
40 Amsterdam UMC - Amsterdam University Medical Center
41 Newcastle University [Newcastle]
42 DISIT - Dipartimento di Scienze e Innovazione Tecnologica [Alessandria]
43 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
44 Hospital Universitario Marqués de Valdecilla [Santander]
45 UNIMIB - Università degli Studi di Milano-Bicocca = University of Milano-Bicocca
46 Human Tumor Immunobiology Unit [Fondazione IRCCS Istituto Nazionale dei Tumori, Milan]
47 DEÜ - Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir]
48 UNIPR - Università degli studi di Parma = University of Parma
49 IPP PRAGUE - Institute of Plasma Physics, Association EURATOM
50 UFRJ - Universidade Federal do Rio de Janeiro [Brasil] = Federal University of Rio de Janeiro [Brazil] = Université fédérale de Rio de Janeiro [Brésil]
51 University of Belgrade [Belgrade]
52 Marmara University [Kadıköy - İstanbul]
53 UniBs - Università degli Studi di Brescia = University of Brescia
54 Universidad de Burgos
55 Unicatt - Università cattolica del Sacro Cuore [Milano]
56 Uninsubria - Universitá degli Studi dell’Insubria = University of Insubria [Varese]
57 King‘s College London
58 UNIMI - Università degli Studi di Milano = University of Milan
59 UC San Diego - University of California [San Diego]
60 University of Cologne
61 Clinique Turin

Limited data have been published on the epidemiology and outcomes of breakthrough COVID-19 in patients with hematological malignancy (HM) after anti-SARS-CoV-2 vaccination. Adult HM who received at least one dose of anti-SARS-CoV-2 vaccine and diagnosed with breakthrough COVID-19 between January 2021 and March 2022 and registered in EPICOVIDEHA were included in this analysis. A total of 1548 cases were included, mainly with lymphoid malignancies (1181 cases, 76%). After viral genome sequencing in 753 cases (49%), Omicron variant was prevalent (517, 68.7%). Most of the patients received at least two vaccine doses before COVID-19 (1419, 91%), mostly mRNA-based (1377, 89%). Overall, 906 patients (59%) received specific treatment for COVID-19. After 30-days follow-up from COVID-19 diagnosis, 143 patients (9%) died. The mortality rate in patients with Omicron variant was of 7.9%, comparable to that reported for the other variants. The 30-day mortality rate was significantly lower than in the pre-vaccine era (31%). In the univariable analysis, older age (p<0.001), active HM (p<0.001), severe and critical COVID-19 (p=0.007 and p<0.001, respectively) were associated with mortality. Conversely, patients receiving monoclonal antibodies, even for severe or critical COVID-19, had a lower mortality rate (p<0.001). In the multivariable model, older age, active disease, critical COVID-19 and at least 2-3 comorbidities were correlated with a higher mortality, whereas the administration of monoclonal antibodies, alone (p<0.001) or combined with antivirals (p=0.009), was observed protective. While mortality is significantly lower than in the pre-vaccination era, breakthrough COVID-19 in HM is still associated with considerable mortality. Death rate was lower in patients who received monoclonal antibodies, alone or in combination with antivirals. EPICOVIDEHA (www.clinicaltrials.gov; National Clinical Trials identifier NCT04733729) is an international open web-based registry for patients with HMs infected with SARS-CoV-2.

Domaines: Immunologie; Cancer; Hématologie

Livio Pagano, Jon Salmanton-García, Francesco Marchesi, Ola Blennow, Maria Gomes da Silva, et al.. Breakthrough COVID-19 in vaccinated patients with hematologic malignancies: results from EPICOVIDEHA survey. Blood, 2022, ⟨10.1182/blood.2022017257/1922289/blood.2022017257.pdf⟩. ⟨hal-03791153⟩