Nirmatrelvir/ritonavir in COVID-19 patients with haematological malignancies: a report from the EPICOVIDEHA registry

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Salmanton-García, Jon | Marchesi, F. | Gomes da Silva, Maria | Farina, Francesca | Dávila-Valls, Julio | Bilgin, Yavuz M. | Glenthøj, Andreas Birkedal | Falces-Romero, Iker | van Doesum, Jaap A. | Labrador, Jorge | Buquicchio, Caterina | El-Ashwah, Shaimaa Saber | Petzer, Verena | van Praet, Jens T. | Schönlein, Martin | Dargenio, Michelina | Méndez, Gustavo Adolfo | Meers, Stef | Itri, Federico | Giordano, Antonio | Pinczés, László Imre | Espigado, Ildefonso | Stojanoski, Zlate | López-García, Alberto | Prezioso, Lucia | Jaksic, Ozren | Vena, Antonio | Fracchiolla, Nicola Stefano | González-López, Tomás José | Colović, Nataša R. | Delia, Mario | Weinbergerová, Barbora | Marchetti, Monia | Marques de Almeida, Joyce | Finizio, Olimpia | Besson, Caroline M. | Biernat, Monika Maria | Valković, Toni | Lahmer, Tobias | Cuccaro, Annarosa | Ormazabal-Vélez, Irati | Batinić, Josip | Fernández, Noemí Llamas | de Jonge, Nick A. | Tascini, Carlo | Anastasopoulou, Amalia N. | Duléry, Rémy | del Principe, Maria Ilaria | Plantefeve, Gaétan J. | Papa, M. V. | Nucci, Márcio Luiz Moore | Jiménez, María Moraima | Aujayeb, Avinash | Hernández-Rivas, José Ángel | Merelli, M. | Cattaneo, Chiara | Blennow, Ola | Nordlander, Anna | Cabirta, Alba | Varricchio, Gina | Sacchi, Maria Vittoria | Cordoba, Raúl | Arellano, Elena | Gräfe, Stefanie K. | Wolf, Dominik G. | Emarah, Ziad A. | Ammatuna, Emanuele | Hersby, Ditte Stampe | Martín-Pérez, Sonia | Nunes Rodrigues, Raquel | Rahimli, Laman | Pagano, Livio | Cornely, Oliver A. | Piukovics, Klára | de Ramón, Cristina | Danion, François | Yahya, Ayel | Guidetti, Anna | Garcia-Vidal, Carolina | Sili, Uluhan | Meletiadis, Joseph | de Kort, Elizabeth A. | Verga, Luisa | Serrano, Laura | Erben, N. | Di Blasi, Roberta | Tragiannidis, Athanasios | Ribera-Santa Susana, José María | Ommen, Hans Beier | Busca, Alessandro | Coppola, N. | Bergantim, Rui | Dragonetti, Giulia | Criscuolo, Marianna | Fianchi, Luana | Bonanni, Matteo | Soto-Silva, Andrés | Mikulska, Małgorzata Karolina | Machado, Marina L. | Shan Kho, Chi | Hassan, Nazia | Gavriilaki, Eleni | Cordini, Gregorio | Chi, Louis Yi Ann | Eggerer, Matthias | Hoenigl, Martin | Prattes, Juergen | Jiménez-Lorenzo, María Josefa | Zompi, Sofia | Zambrotta, Giovanni Paolo Maria | Çolak, Gökçe Melis | García-Poutón, Nicole | Aiello, Tommaso Francesco | Prin, Romane | Stamouli, Maria I. | Samarkos, Michael

Edité par CCSD ; Elsevier -

International audience. Background: Nirmatrelvir/ritonavir treatment decreases the hospitalisation rate in immunocompetent patients with COVID-19, but data on efficacy in patients with haematological malignancy are scarce. Here, we describe the outcome of nirmatrelvir/ritonavir treatment in a large cohort of the latter patients. Methods: This is a retrospective cohort study from the multicentre EPICOVIDEHA registry (NCT04733729) on patients with haematological malignancy, who were diagnosed with COVID-19 between January and September 2022. Patients receiving nirmatrelvir/ritonavir were compared to those who did not. A logistic regression was run to determine factors associated with nirmatrelvir/ritonavir administration in our sample. Mortality between treatment groups was assessed with Kaplan–Meier survival plots after matching all the patients with a propensity score. Additionally, a Cox regression was modelled to detect factors associated with mortality in patients receiving nirmatrelvir/ritonavir. Findings: A total of 1859 patients were analysed, 117 (6%) were treated with nirmatrelvir/ritonavir, 1742 (94%) were treated otherwise. Of 117 patients receiving nirmatrelvir/ritonavir, 80% had received ≥1 anti-SARS-CoV-2 vaccine dose before COVID-19 onset, 13% of which received a 2nd vaccine booster. 5% were admitted to ICU. Nirmatrelvir/ritonavir treatment was associated with the presence of extrapulmonary symptoms at COVID-19 onset, for example anosmia, fever, rhinitis, or sinusitis (aOR 2.509, 95%CI 1.448–4.347) and 2nd vaccine booster (aOR 3.624, 95%CI 1.619–8.109). Chronic pulmonary disease (aOR 0.261, 95%CI 0.093–0.732) and obesity (aOR 0.105, 95%CI 0.014–0.776) were not associated with nirmatrelvir/ritonavir use. After propensity score matching, day-30 mortality rate in patients treated with nirmatrelvir/ritonavir was 2%, significantly lower than in patients with SARS-CoV-2 directed treatment other than nirmatrelvir/ritonavir (11%, p = 0.036). No factor was observed explaining the mortality difference in patients after nirmatrelvir/ritonavir administration. Interpretation: Haematological malignancy patients were more likely to receive nirmatrelvir/ritonavir when reporting extrapulmonary symptoms or 2nd vaccine booster at COVID-19 onset, as opposed to chronic pulmonary disease and obesity. The mortality rate in patients treated with nirmatrelvir/ritonavir was lower than in patients with targeted drugs other than nirmatrelvir/ritonavir. Funding: EPICOVIDEHA has received funds from Optics COMMIT (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223).

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