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

Livio Pagano, Jon Salmanton-García, Francesco Marchesi, Ola Blennow, Maria Gomes da Silva, Andreas Glenthøj, Jaap van Doesum, Yavuz M Bilgin, Alberto López-García, Federico Itri, Raquel Nunes Rodrigues, Barbora Weinbergerová, Francesca Farina, Giulia Dragonetti, Caroline Berg Venemyr, Jens van Praet, Ozren Jaksic, Toni Valković, Iker Falces-Romero, Sonia Martín-Pérez, Moraima Jiménez, Julio Dávila-Valls, Martin Schönlein, Emanuele Ammatuna, Stef Meers, Mario Delia, Zlate Stojanoski, Anna Nordlander, Tobias Lahmer, László Imre Pinczés, Caterina Buquicchio, Klára Piukovics, Irati Ormazabal-Vélez, Nicola Fracchiolla, Michail Samarkos, Gustavo-Adolfo Méndez, José-Ángel Hernández-Rivas, Ildefonso Espigado, Martin Cernan, Verena Petzer, Sylvain Lamure, Roberta di Blasi, Joyce Marques de Almedia, Michelina Dargenio, Monika M Biernat, Mariarita Sciumè, Cristina de Ramón, Nick de Jonge, Josip Batinić, Avinash Aujayeb, Monia Marchetti, Guillemette Fouquet, Noemí Fernández, Giovanni Zambrotta, Maria Vittoria Sacchi, Anna Guidetti, Fatih Demirkan, Lucia Prezioso, Zdeněk Ráčil, Marcio Nucci, Miloš Mladenović, Raphaël Liévin, Michaela Hanáková, Stefanie Gräfe, Uluhan Sili, Marina Machado, Chiara Cattaneo, Tatjana Adžić-Vukičević, Luisa Verga, Jorge Labrador, Laman Rahimli, Matteo Bonanni, Francesco Passamonti, Antonio Pagliuca, Paolo Corradini, Martin Hoenigl, Philipp Koehler, Alessandro Busca, Oliver A Cornely, Livio Pagano, Jon Salmanton-García, Francesco Marchesi, Ola Blennow, Maria Gomes da Silva, Andreas Glenthøj, Jaap van Doesum, Yavuz M Bilgin, Alberto López-García, Federico Itri, Raquel Nunes Rodrigues, Barbora Weinbergerová, Francesca Farina, Giulia Dragonetti, Caroline Berg Venemyr, Jens van Praet, Ozren Jaksic, Toni Valković, Iker Falces-Romero, Sonia Martín-Pérez, Moraima Jiménez, Julio Dávila-Valls, Martin Schönlein, Emanuele Ammatuna, Stef Meers, Mario Delia, Zlate Stojanoski, Anna Nordlander, Tobias Lahmer, László Imre Pinczés, Caterina Buquicchio, Klára Piukovics, Irati Ormazabal-Vélez, Nicola Fracchiolla, Michail Samarkos, Gustavo-Adolfo Méndez, José-Ángel Hernández-Rivas, Ildefonso Espigado, Martin Cernan, Verena Petzer, Sylvain Lamure, Roberta di Blasi, Joyce Marques de Almedia, Michelina Dargenio, Monika M Biernat, Mariarita Sciumè, Cristina de Ramón, Nick de Jonge, Josip Batinić, Avinash Aujayeb, Monia Marchetti, Guillemette Fouquet, Noemí Fernández, Giovanni Zambrotta, Maria Vittoria Sacchi, Anna Guidetti, Fatih Demirkan, Lucia Prezioso, Zdeněk Ráčil, Marcio Nucci, Miloš Mladenović, Raphaël Liévin, Michaela Hanáková, Stefanie Gräfe, Uluhan Sili, Marina Machado, Chiara Cattaneo, Tatjana Adžić-Vukičević, Luisa Verga, Jorge Labrador, Laman Rahimli, Matteo Bonanni, Francesco Passamonti, Antonio Pagliuca, Paolo Corradini, Martin Hoenigl, Philipp Koehler, Alessandro Busca, Oliver A Cornely

Abstract

Limited data are available on breakthrough COVID-19 in patients with hematologic malignancy (HM) after anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Adult patients with HM, ≥1 dose of anti-SARS-CoV-2 vaccine, and breakthrough COVID-19 between January 2021 and March 2022 were analyzed. A total of 1548 cases were included, mainly lymphoid malignancies (1181 cases, 76%). After viral sequencing in 753 cases (49%), the Omicron variant was prevalent (517, 68.7%). Most of the patients received ≤2 vaccine doses before COVID-19 (1419, 91%), mostly mRNA-based (1377, 89%). Overall, 906 patients (59%) received COVID-19-specific treatment. After 30-day follow-up from COVID-19 diagnosis, 143 patients (9%) died. The mortality rate in patients with the Omicron variant was 7.9%, comparable to other variants, with a significantly lower 30-day mortality rate than in the prevaccine era (31%). In the univariable analysis, older age (P < .001), active HM (P < .001), and severe and critical COVID-19 (P = .007 and P < .001, respectively) were associated with mortality. Conversely, patients receiving monoclonal antibodies, even for severe or critical COVID-19, had a lower mortality rate (P < .001). In the multivariable model, older age, active disease, critical COVID-19, and 2-3 comorbidities were correlated with a higher mortality, whereas monoclonal antibody administration, alone (P < .001) or combined with antivirals (P = .009), was protective. Although mortality is significantly lower than in the prevaccination 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.

Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

A complete list of the EPICOVIDEHA Survey collaborators appears in “Appendix.”

© 2022 by The American Society of Hematology.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
Patient distribution by serological response after last COVID-19 vaccination before COVID-19 diagnosis. (A) By baseline malignancy; (B) by last treatment for HM immediately before COVID-19 diagnosis.
Figure 2.
Figure 2.
Survival probability by most prevalent underlying condition.
Figure 3.
Figure 3.
Survival probability of patients by COVID-19 treatment.
Figure 4.
Figure 4.
Survival probability by COVID-19 treatment and COVID-19 severity. (A) Patients who were asymptomatic; (B) patients with mild disease; (C) patients with severe disease; and (D) patients who were critically ill.
Figure 5.
Figure 5.
Survival probability by SARS-CoV-2 variant.
Figure 6.
Figure 6.
Patient distribution by number of SARS-CoV-2 vaccination doses administered before COVID-19 diagnosis, and COVID-19 severity.

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