Nirmatrelvir/ritonavir in COVID-19 patients with haematological malignancies: a report from the EPICOVIDEHA registry
Status PubMed-not-MEDLINE Language English Country England, Great Britain Media print-electronic
Document type Journal Article
PubMed
37041967
PubMed Central
PMC10078172
DOI
10.1016/j.eclinm.2023.101939
PII: S2589-5370(23)00116-5
Knihovny.cz E-resources
- Keywords
- COVID-19, Haematology, Malignancy, Nirmatrelvir, SARS-CoV-2,
- Publication type
- Journal Article MeSH
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).
1 Department of Medicine University Medical Center Hamburg Eppendorf Hamburg Germany
3 Department of Medicine University Medical Center Hamburg Eppendorf Hamburg Germany
Amsterdam UMC Location VUmc Amsterdam the Netherlands
Azienda Ospedaliera Nazionale SS Antonio e Biagio e Cesare Arrigo Alessandria Italy
Azienda Ospedaliera Sant'Anna e San Sebastiano Caserta Italy
Azienda Sanitaria Universitaria del Friuli Centrale Udine Italy
Centre Hospitalier de Versailles Le Chesnay France
CIBERINFEC Instituto de Salud Carlos 3 Madrid Spain
Complejo Hospitalario de Navarra Iruña Pamplona Spain
Croatian Cooperative Group for Hematological Diseases Croatia
Departament de Medicina Universitat Autònoma de Barcelona Bellaterra Spain
Department of Hematology and Oncology Comprehensive Cancer Center Innsbruck Innsbruck Austria
Department of Hematology Copenhagen University Hospital Rigshospitalet Copenhagen Denmark
Department of Hematology Hospital Universitario de Burgos Burgos Spain
Department of Hematology Research Unit Hospital Universitario de Burgos Burgos Spain
Department of Hematology University Hospital Dubrava Zagreb Croatia
Department of Hematology University Hospital Virgen Macarena Seville Spain
Department of Infectious Diseases Karolinska University Hospital Stockholm Sweden
Department of Internal Medicine ADRZ Goes the Netherlands
Department of Nephrology and Infectious Diseases AZ Sint Jan Brugge Oostende AV Brugge Belgium
Departmento de Medicina Universidad Complutense de Madrid Madrid Spain
Ematologia con Trapianto Ospedale Dimiccoli Barletta Barletta Italy
Facultad de Ciencias de la Salud Universidad Isabel 1 Burgos Spain
Faculty of Medicine and Faculty of Health Studies University of Rijeka Rijeka Croatia
Federal University of Rio de Janeiro Rio de Janeiro Brazil
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy
Fundacion Jimenez Diaz University Hospital Health Research Institute IIS FJD Madrid Spain
German Centre for Infection Research Partner Site Bonn Cologne Cologne Germany
Head ICU and CRC Centre Hospitalier Victor DUPOUY Argenteuil France
Hematology and Stem Cell Transplant Unit IRCCS Regina Elena National Cancer Institute Rome Italy
Hematology and Stem Cell Transplant Unit Vito Fazzi Lecce Italy
Hematology and Stem Cell Transplantation Unit AOUC Policlinico Bari Italy
Hematology Department of Biomedicine and Prevention University of Rome Tor Vergata Rome Italy
Hematology Unit ASST Spedali Civili Brescia Italy
Hematology Unit Center for Translational Medicine Azienda USL Toscana NordOvest Livorno Italy
Hematology Unit Fondazione Policlinico Universitario Agostino Gemelli IRCCS Rome Italy
Hematology Unit Università Cattolica del Sacro Cuore Rome Italy
Hospital Escuela de Agudos Dr Ramón Madariaga Posadas Argentina
Hospital Nuestra Señora de Sonsoles Ávila Spain
Hospital Universitario Infanta Leonor Madrid Spain
Hospital Universitario Marqués de Valdecilla Santander Spain
Hospital University of Parma Hematology and Bone Marrow Unit Parma Italy
IRCCS Ospedale San Raffaele Milan Italy
Istituto Oncologico della Svizzera Italiana Bellinzona Switzerland
La Paz University Hospital Madrid Spain
Laikon Hospital Medical School National and Kapodistrian University of Athens Athens Greece
Medizinische Klinik 2 Klinikum rechts der Isar TU München Munich Germany
Northumbria Healthcare Newcastle United Kingdom
Oncology Center Mansoura University Mansoura Egypt
Ospedale Policlinico San Martino Genoa Italy
Portuguese Institute of Oncology Lisbon Portugal
San Luigi Gonzaga Hospital Orbassano Orbassano Italy
School of Medicine University of Zagreb Zagreb Croatia
Université Paris Saclay UVSQ Inserm Équipe Exposome et Hérédité CESP Villejuif France
University Clinic of Hematology Skopje North Macedonia
University Clinical Center Serbia Medical Faculty University Belgrade Belgrade Serbia
University Hospital Centre Rijeka Rijeka Croatia
University Hospital Centre Zagreb Zagreb Croatia
University Medical Center Groningen Groningen the Netherlands
See more in PubMed
Mahase E. Covid-19: WHO declares pandemic because of "alarming levels" of spread, severity, and inaction. BMJ. 2020;368:m1036. PubMed
Baden L.R., El Sahly H.M., Essink B., et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403–416. PubMed PMC
Polack F.P., Thomas S.J., Kitchin N., et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383(27):2603–2615. PubMed PMC
Pagano L., Salmanton-Garcia J., Marchesi F., et al. Breakthrough COVID-19 in vaccinated patients with hematologic malignancies: results from EPICOVIDEHA survey. Blood. 2022;140(26):2773–2787. doi: 10.1182/blood.2022017257. PubMed DOI PMC
Pagano L., Salmanton-Garcia J., Marchesi F., et al. COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA) J Hematol Oncol. 2021;14(1):168. PubMed PMC
Pagano L., Salmanton-Garcia J., Marchesi F., et al. COVID-19 in vaccinated adult patients with hematological malignancies: preliminary results from EPICOVIDEHA. Blood. 2022;139(10):1588–1592. PubMed PMC
Fischer W.A., 2nd, Eron J.J., Jr., Holman W., et al. A phase 2a clinical trial of molnupiravir in patients with COVID-19 shows accelerated SARS-CoV-2 RNA clearance and elimination of infectious virus. Sci Transl Med. 2022;14(628) PubMed PMC
Hammond J., Leister-Tebbe H., Gardner A., et al. Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19. N Engl J Med. 2022;386(15):1397–1408. PubMed PMC
Beigel J.H., Tomashek K.M., Dodd L.E., et al. Remdesivir for the treatment of Covid-19 - final report. N Engl J Med. 2020;383(19):1813–1826. PubMed PMC
Gottlieb R.L., Nirula A., Chen P., et al. Effect of bamlanivimab as monotherapy or in combination with etesevimab on viral load in patients with mild to moderate COVID-19: a randomized clinical trial. JAMA. 2021;325(7):632–644. PubMed PMC
O'Brien M.P., Forleo-Neto E., Sarkar N., et al. Effect of subcutaneous Casirivimab and imdevimab antibody combination vs placebo on development of symptomatic COVID-19 in early asymptomatic SARS-CoV-2 infection: a randomized clinical trial. JAMA. 2022;327(5):432–441. PubMed PMC
Kim J.Y., Sandulescu O., Preotescu L.L., et al. A randomized clinical trial of regdanvimab in high-risk patients with mild-to-moderate coronavirus disease 2019. Open Forum Infect Dis. 2022;9(8):ofac406. PubMed PMC
Group AC-TfIwC-S Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial. Lancet Infect Dis. 2022;22(5):622–635. PubMed PMC
Group AC--TfIwC- S. Tixagevimab-cilgavimab for treatment of patients hospitalised with COVID-19: a randomised, double-blind, phase 3 trial. Lancet Respir Med. 2022;10(10):972–984. PubMed PMC
U.S. Food and Drug Administration Fact sheet for healthcare providers: emergency use authorization for paxlovid. 2022. https://www.fda.gov/media/155050/download
European Medicine Agency Paxlovid. 2022. https://www.ema.europa.eu/en/medicines/human/EPAR/paxlovid
Cesaro S., Ljungman P., Mikulska M., et al. Recommendations for the management of COVID-19 in patients with haematological malignancies or haematopoietic cell transplantation, from the 2021 European Conference on Infections in Leukaemia (ECIL 9) Leukemia. 2022;36(6):1467–1480. PubMed PMC
Sun F., Lin Y., Wang X., Gao Y., Ye S. Paxlovid in patients who are immunocompromised and hospitalised with SARS-CoV-2 infection. Lancet Infect Dis. 2022;22(9):1279. PubMed PMC
Salmanton-Garcia J., Busca A., Cornely O.A., et al. EPICOVIDEHA: a ready to use platform for epidemiological studies in hematological patients with COVID-19. Hemasphere. 2021;5(7):e612. PubMed PMC
Santos V.B.D., Stein A.T., Barilli S.L.S., et al. Adult patients admitted to a tertiary hospital for COVID-19 and risk factors associated with severity: a retrospective cohort study. Rev Inst Med Trop Sao Paulo. 2022;64 PubMed PMC
Zimmermann G.W. Paxlovid™ jetzt direkt an Patienten abgeben. MMW Fortschr Med. 2022;164(15):31. PubMed PMC
Birabaharan M., Martin T.C.S. Acute pulmonary emboli following rebound phenomenon after Nirmatrelvir/Ritonavir treatment for COVID-19. Am J Emerg Med. 2022;61:235.e5–235.e6. PubMed PMC
McIntyre P.B., Aggarwal R., Jani I., et al. COVID-19 vaccine strategies must focus on severe disease and global equity. Lancet. 2022;399(10322):406–410. PubMed PMC
European Centre for Disease Prevention and Control Uptake of the primary course of COVID-19 vaccination among the total population in EU/EEA countries as of 16 October 2022. 2022. https://covid19-country-overviews.ecdc.europa.eu/vaccination.html
Nguyen M., Bain N., Grech L., et al. COVID-19 vaccination rates, intent, and hesitancy in patients with solid organ and blood cancers: a multicenter study. Asia Pac J Clin Oncol. 2022;18(6):570–577. doi: 10.1111/ajco.13754. PubMed DOI
Fishbane S., Hirsch J.S., Nair V. Special Considerations for paxlovid treatment among transplant recipients with SARS-CoV-2 infection. Am J Kidney Dis. 2022;79(4):480–482. PubMed PMC
Berar Yanay N., Bogner I., Saker K., Tannous E. Paxlovid-tacrolimus drug-drug interaction in a 23-year-old female kidney transplant patient with COVID-19. Clin Drug Investig. 2022;42(8):693–695. PubMed PMC
Gold J.A.W., Kelleher J., Magid J., et al. Dispensing of oral antiviral drugs for treatment of COVID-19 by zip code-level social vulnerability - United States, December 23, 2021-May 21, 2022. MMWR Morb Mortal Wkly Rep. 2022;71(25):825–829. PubMed
Najjar-Debbiny R., Gronich N., Weber G., et al. Effectiveness of paxlovid in reducing severe COVID-19 and mortality in high risk patients. Clin Infect Dis. 2023;76(3):e342–e349. doi: 10.1093/cid/ciac443. PubMed DOI PMC
