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

COVID-19 Haematology Malignancy Nirmatrelvir SARS-CoV-2

Journal

EClinicalMedicine
ISSN: 2589-5370
Titre abrégé: EClinicalMedicine
Pays: England
ID NLM: 101733727

Informations de publication

Date de publication:
Apr 2023
Historique:
received: 29 11 2022
revised: 15 03 2023
accepted: 15 03 2023
medline: 13 4 2023
entrez: 12 4 2023
pubmed: 13 4 2023
Statut: ppublish

Résumé

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. 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. 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. 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. 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).

Sections du résumé

Background UNASSIGNED
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 UNASSIGNED
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 UNASSIGNED
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 UNASSIGNED
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 UNASSIGNED
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).

Identifiants

pubmed: 37041967
doi: 10.1016/j.eclinm.2023.101939
pii: S2589-5370(23)00116-5
pmc: PMC10078172
doi:

Types de publication

Journal Article

Langues

eng

Pagination

101939

Investigateurs

Klára Piukovics (K)
Cristina De Ramón (C)
François Danion (F)
Ayel Yahya (A)
Anna Guidetti (A)
Carolina Garcia-Vidal (C)
Uluhan Sili (U)
Joseph Meletiadis (J)
Elizabeth De Kort (E)
Luisa Verga (L)
Laura Serrano (L)
Nurettin Erben (N)
Roberta Di Blasi (R)
Athanasios Tragiannidis (A)
José-María Ribera-Santa Susana (JM)
Hans-Beier Ommen (HB)
Alessandro Busca (A)
Nicola Coppola (N)
Rui Bergantim (R)
Giulia Dragonetti (G)
Marianna Criscuolo (M)
Luana Fianchi (L)
Matteo Bonanni (M)
Andrés Soto-Silva (A)
Malgorzata Mikulska (M)
Marina Machado (M)
Chi Shan Kho (C)
Nazia Hassan (N)
Eleni Gavriilaki (E)
Gregorio Cordini (G)
Louis Yi Ann Chi (LYA)
Matthias Eggerer (M)
Martin Hoenigl (M)
Juergen Prattes (J)
María-Josefa Jiménez-Lorenzo (MJ)
Sofia Zompi (S)
Giovanni Paolo Maria Zambrotta (GPM)
Gökçe Melis Çolak (GM)
Nicole García-Poutón (N)
Tommaso Francesco Aiello (TF)
Romane Prin (R)
Maria Stamouli (M)
Michail Samarkos (M)

Informations de copyright

© 2023 The Author(s).

Déclaration de conflit d'intérêts

The authors do not declare conflicts of interest related to the submitted manuscript. The funder of the study had no role in study design, data analysis, interpretation, or writing of the report. All authors had full access to the data and had final responsibility for the decision to submit for publication.

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Auteurs

Jon Salmanton-García (J)

University of Cologne, Faculty of Medicine, and University Hospital Cologne, Chair Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.
University of Cologne, Faculty of Medicine, and University Hospital Cologne, Department I of Internal Medicine, Excellence Center for Medical Mycology (ECMM), Cologne, Germany.
German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany.

Francesco Marchesi (F)

Hematology and Stem Cell Transplant Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.

Maria Gomes da Silva (M)

Portuguese Institute of Oncology, Lisbon, Portugal.

Francesca Farina (F)

IRCCS Ospedale San Raffaele, Milan, Italy.

Julio Dávila-Valls (J)

Hospital Nuestra Señora de Sonsoles, Ávila, Spain.

Yavuz M Bilgin (YM)

Department of Internal Medicine, ADRZ, Goes, the Netherlands.

Andreas Glenthøj (A)

Department of Hematology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.

Iker Falces-Romero (I)

La Paz University Hospital, Madrid, Spain.
CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain.

Jaap Van Doesum (J)

University Medical Center Groningen, Groningen, the Netherlands.

Jorge Labrador (J)

Department of Hematology, Research Unit, Hospital Universitario de Burgos, Burgos, Spain.
Facultad de Ciencias de la Salud, Universidad Isabel I, Burgos, Spain.

Caterina Buquicchio (C)

Ematologia con Trapianto, Ospedale Dimiccoli Barletta, Barletta, Italy.

Shaimaa El-Ashwah (S)

Oncology Center, Mansoura University, Mansoura, Egypt.

Verena Petzer (V)

Department of Hematology and Oncology, Comprehensive Cancer Center Innsbruck (CCCI), Medical University of Innsbruck (MUI), Innsbruck, Austria.

Jens Van Praet (J)

Department of Nephrology and Infectious Diseases, AZ Sint-Jan Brugge-Oostende AV, Brugge, Belgium.

Martin Schönlein (M)

Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Michelina Dargenio (M)

Hematology and Stem Cell Transplant Unit, Vito Fazzi, Lecce, Italy.

Gustavo-Adolfo Méndez (GA)

Hospital Escuela de Agudos Dr. Ramón Madariaga, Posadas, Argentina.

Stef Meers (S)

AZ KLINA, Brasschaat, Belgium.

Federico Itri (F)

San Luigi Gonzaga Hospital - Orbassano, Orbassano, Italy.

Antonio Giordano (A)

Hematology Unit, Fondazione Policlinico Universitario Agostino Gemelli - IRCCS, Rome, Italy.

László Imre Pinczés (LI)

Division of Hematology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

Ildefonso Espigado (I)

Department of Hematology, University Hospital Virgen Macarena - University Hospital Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS / CSIC), Universidad de Sevilla (Departamento de Medicina), Seville, Spain.

Zlate Stojanoski (Z)

University Clinic of Hematology, Skopje, North Macedonia.

Alberto López-García (A)

Fundacion Jimenez Diaz University Hospital, Health Research Institute IIS-FJD, Madrid, Spain.

Lucia Prezioso (L)

Hospital University of Parma - Hematology and Bone Marrow Unit, Parma, Italy.

Ozren Jaksic (O)

Department of Hematology, University Hospital Dubrava, Zagreb, Croatia.

Antonio Vena (A)

Ospedale Policlinico San Martino, Genoa, Italy.

Nicola S Fracchiolla (NS)

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Tomás José González-López (TJ)

Department of Hematology, Hospital Universitario de Burgos, Burgos, Spain.

Natasa Colović (N)

University Clinical Center Serbia, Medical Faculty University Belgrade, Belgrade, Serbia.

Mario Delia (M)

Hematology and Stem Cell Transplantation Unit, AOUC Policlinico, Bari, Italy.

Barbora Weinbergerová (B)

Department of Internal Medicine - Hematology and Oncology, Masaryk University Hospital Brno, Brno, Czech Republic.

Monia Marchetti (M)

Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy.

Joyce Marques de Almeida (J)

Istituto Oncologico della Svizzera Italiana, Bellinzona, Switzerland.

Olimpia Finizio (O)

UOC Hematology, AORN Cardarelli, Naples, Italy.

Caroline Besson (C)

Centre Hospitalier de Versailles, Le Chesnay, France.
Université Paris-Saclay, UVSQ, Inserm, Équipe "Exposome et Hérédité", CESP, Villejuif, France.

Monika M Biernat (MM)

Department of Haematology, Blood Neoplasms, and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland.

Toni Valković (T)

University Hospital Centre Rijeka, Rijeka, Croatia.
Croatian Cooperative Group for Hematological Diseases (CROHEM), Croatia.
Faculty of Medicine and Faculty of Health Studies University of Rijeka, Rijeka, Croatia.

Tobias Lahmer (T)

Medizinische Klinik II, Klinikum rechts der Isar, TU München, Munich, Germany.

Annarosa Cuccaro (A)

Hematology Unit, Center for Translational Medicine, Azienda USL Toscana NordOvest, Livorno, Italy.

Irati Ormazabal-Vélez (I)

Complejo Hospitalario de Navarra, Iruña-Pamplona, Spain.

Josip Batinić (J)

University Hospital Centre Zagreb, Zagreb, Croatia.
School of Medicine University of Zagreb, Zagreb, Croatia.

Noemí Fernández (N)

Hospital Universitario Marqués de Valdecilla, Santander, Spain.

Nick De Jonge (N)

Amsterdam UMC, Location VUmc, Amsterdam, the Netherlands.

Carlo Tascini (C)

Azienda Sanitaria Universitaria del Friuli Centrale, Udine, Italy.

Amalia N Anastasopoulou (AN)

Laikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Rémy Duléry (R)

Service d'Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Inserm UMRs 938, Paris, France.

Maria Ilaria Del Principe (MI)

Hematology, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.

Gaëtan Plantefeve (G)

Head ICU and CRC, Centre Hospitalier Victor DUPOUY, Argenteuil, France.

Mario Virgilio Papa (MV)

Azienda Ospedaliera Sant'Anna e San Sebastiano, Caserta, Italy.

Marcio Nucci (M)

Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

Moraima Jiménez (M)

Department of Hematology, Vall d'Hebron Hospital Universitari, Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.

Avinash Aujayeb (A)

Northumbria Healthcare, Newcastle, United Kingdom.

José-Ángel Hernández-Rivas (JÁ)

Hospital Universitario Infanta Leonor, Madrid, Spain.
Departmento de Medicina, Universidad Complutense de Madrid, Madrid, Spain.

Maria Merelli (M)

Azienda Sanitaria Universitaria del Friuli Centrale, Udine, Italy.

Chiara Cattaneo (C)

Hematology Unit, ASST-Spedali Civili, Brescia, Italy.

Ola Blennow (O)

Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.

Anna Nordlander (A)

Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.

Alba Cabirta (A)

Department of Hematology, Vall d'Hebron Hospital Universitari, Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.

Gina Varricchio (G)

Azienda Ospedaliera Sant'Anna e San Sebastiano, Caserta, Italy.

Maria Vittoria Sacchi (MV)

Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy.

Raul Cordoba (R)

Fundacion Jimenez Diaz University Hospital, Health Research Institute IIS-FJD, Madrid, Spain.

Elena Arellano (E)

Department of Hematology, University Hospital Virgen Macarena, Seville, Spain.

Stefanie K Gräfe (SK)

University of Cologne, Faculty of Medicine, and University Hospital Cologne, Department I of Internal Medicine, Excellence Center for Medical Mycology (ECMM), Cologne, Germany.
I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
University of Cologne, Faculty of Medicine, and University Hospital Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.

Dominik Wolf (D)

Department of Hematology and Oncology, Comprehensive Cancer Center Innsbruck (CCCI), Medical University of Innsbruck (MUI), Innsbruck, Austria.

Ziad Emarah (Z)

Oncology Center, Mansoura University, Mansoura, Egypt.

Emanuele Ammatuna (E)

University Medical Center Groningen, Groningen, the Netherlands.

Ditte Stampe Hersby (DS)

Department of Hematology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.

Sonia Martín-Pérez (S)

Hospital Nuestra Señora de Sonsoles, Ávila, Spain.

Raquel Nunes Rodrigues (R)

Portuguese Institute of Oncology, Lisbon, Portugal.

Laman Rahimli (L)

University of Cologne, Faculty of Medicine, and University Hospital Cologne, Department I of Internal Medicine, Excellence Center for Medical Mycology (ECMM), Cologne, Germany.
University of Cologne, Faculty of Medicine, and University Hospital Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.

Livio Pagano (L)

Hematology Unit, Fondazione Policlinico Universitario Agostino Gemelli - IRCCS, Rome, Italy.
Hematology Unit, Università Cattolica del Sacro Cuore, Rome, Italy.

Oliver A Cornely (OA)

University of Cologne, Faculty of Medicine, and University Hospital Cologne, Chair Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.
University of Cologne, Faculty of Medicine, and University Hospital Cologne, Department I of Internal Medicine, Excellence Center for Medical Mycology (ECMM), Cologne, Germany.
German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany.
University of Cologne, Faculty of Medicine, and University Hospital Cologne, Center for Molecular Medicine Cologne (CMMC), Cologne, Germany.
University of Cologne, Faculty of Medicine, and University Hospital Cologne, Clinical Trials Centre Cologne (ZKS Köln), Cologne, Germany.

Classifications MeSH