EClinicalMedicine (Apr 2023)

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

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

Journal volume & issue
Vol. 58
p. 101939

Abstract

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Summary: 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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