Molnupiravir compared to nirmatrelvir/ritonavir for COVID-19 in high-risk patients with haematological malignancy in Europe. A matched-paired analysis from the EPICOVIDEHA registry

  • Jon Salmanton-García (Shared first author)
  • Francesco Marchesi (Shared first author)
  • Philipp Koehler
  • Barbora Weinbergerová
  • Natasa Čolović
  • Iker Falces-Romero
  • Caterina Buquicchio
  • Francesca Farina
  • Jens van Praet
  • Monika M Biernat
  • Federico Itri
  • Lucia Prezioso
  • Carlo Tascini
  • Antonio Vena
  • Alessandra Romano
  • Mario Delia
  • Sonia Martín-Pérez
  • Esperanza Lavilla-Rubira
  • Tatjana Adžić-Vukičević
  • Daniel García-Bordallo
  • Alberto López-García
  • Mariana Criscuolo
  • Verena Petzer
  • Nicola S Fracchiolla
  • Ildefonso Espigado
  • Uluhan Sili
  • Stef Meers
  • Nurettin Erben
  • Athanasios Tragiannidis
  • Eleni Gavriilaki
  • Martin Schönlein
  • Mirjana Mitrovic
  • Nikola Pantic
  • Maria Merelli
  • Jorge Labrador
  • José-Ángel Hernández-Rivas
  • Andreas Glenthøj
  • Guillemette Fouquet
  • Maria Ilaria Del Principe
  • Michelina Dargenio
  • María Calbacho
  • Caroline Besson
  • Milena Kohn
  • Stefanie Gräfe
  • Ditte Stampe Hersby
  • Elena Arellano
  • Gökçe Melis Çolak
  • Dominik Wolf
  • Monia Marchetti
  • Anna Nordlander
  • Ola Blennow
  • Raul Cordoba
  • Bojana Mišković
  • Miloš Mladenović
  • Martina Bavastro
  • Alessandro Limongelli
  • Laman Rahimli
  • Livio Pagano (Shared last author)
  • Oliver A Cornely (Shared last author)

Abstract

INTRODUCTION: Molnupiravir and nirmatrelvir/ritonavir are antivirals used to prevent progression to severe SARS-CoV-2 infections and decrease hospitalisation and mortality rates. Nirmatrelvir/ritonavir was authorised in Europe in December 2021, whereas molnupiravir is not yet licensed in Europe as of February 2022. Molnupiravir may be an alternative to nirmatrelvir/ritonavir because it is associated with fewer drug-drug interactions and contraindications. A caveat for molnupiravir is the mode of action induces viral mutations. Mortality rate reduction with molnupiravir was less pronounced than that with nirmatrelvir/ritonavir in patients without haematological malignancy. Little is known about the comparative efficacy of the two drugs in patients with haematological malignancy at high-risk of severe COVID-19. Thus, molnupiravir and nirmatrelvir/ritonavir were compared in a cohort of patients with haematological malignancies.

METHODS: Clinical data from patients treated with molnupiravir or nirmatrelvir/ritonavir monotherapy for COVID-19 were retrieved from the EPICOVIDEHA registry. Patients treated with molnupiravir were matched by sex, age (±10 years), and severity of baseline haematological malignancy to controls treated with nirmatrelvir/ritonavir.

RESULTS: A total of 116 patients receiving molnupiravir for the clinical management of COVID-19 were matched to an equal number of controls receiving nirmatrelvir/ritonavir. In each of the groups, 68 (59%) patients were male; with a median age of 64 years (interquartile range [IQR] 53-74) for molnupiravir recipients and 64 years (IQR 54-73) for nirmatrelvir/ritonavir recipients; 56.9% (n=66) of the patients had controlled baseline haematological malignancy, 12.9% (n=15) had stable disease, and 30.2% (n=35) had active disease at COVID-19 onset in each group. During COVID-19 infection, one third of patients from each group were admitted to hospital. Although a similar proportion of patients in the two groups were vaccinated (molnupiravir n=77, 66% vs. nirmatrelvir/ritonavir n=87, 75%), more of those treated with nirmatrelvir/ritonavir had received four vaccine doses (n=27, 23%) compared with those treated with molnupiravir (n=5, 4%) (P<0.001). No differences were detected in COVID-19 severity (P=0.39) or hospitalisation (P=1.0). No statistically significant differences were identified in overall mortality rate (P=0.78) or survival probability (d30 P=0.19, d60 P=0.67, d90 P=0.68, last day of follow up P=0.68). Deaths were either attributed to COVID-19, or the infection was judged by the treating physician to have contributed to death.

CONCLUSIONS: Hospitalisation and mortality rates with molnupiravir were comparable to those with nirmatrelvir/ritonavir in high-risk patients with haematological malignancies and COVID-19. Molnupiravir is a plausible alternative to nirmatrelvir/ritonavir for COVID-19 treatment in patients with haematological malignancy.

Bibliographical data

Original languageEnglish
ISSN0924-8579
DOIs
Publication statusPublished - 10.2023

Comment Deanary

Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.

PubMed 37582478