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

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Molnupiravir and nirmatrelvir/ritonavir are antivirals aiming to prevent the development of severe forms of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Nirmatrelvir/ritonavir was authorised in Europe in December 2021. Molnupiravir is not yet licensed in Europe. Molnupiravir may be an alternative to nirmatrelvir/ritonavir, because of less frequent adverse reactions and fewer drug-drug interactions. Little is known about comparative efficacy of the two drugs in patients with haematological malignancy (HM) at high-risk of severe COVID-19. Aims: We aimed to assess the effectiveness of molnupiravir compared to nirmatrelvir/ritonavir in our HM patient cohort. Methods: Clinical data of patients treated either with molnupiravir or nirmatrelvir/ritonavir monotherapies for COVID-19 were retrieved from the EPICOVIDEHA registry. Patients treated with molnupiravir were matched in sex, age (±5 years), baseline HM severity and hospital admission to controls treated with nirmatrelvir/ritonavir. Results: A total of 108 patients receiving molnupiravir for the clinical management of COVID-19 were matched to an equal number of controls receiving nirmatrelvir/ritonavir. Patients under molnupiravir treatment had a higher prevalence of lymphopenia (lymphocytes count <201 cells/µl, n=16, 15%) as compared to those under nirmatrelvir/ritonavir (n=6, 6%, p=0.025). Although a similar proportion of vaccinated patients was observed in both groups (molnupiravir n=73, 68% vs nirmatrelvir/ritonavir n=76, 70%), those under nirmatrelvir/ritonavir more often had received four doses (n=21, 19%) as compared to the ones under molnupiravir (n=4, 4%, p=0.002). Nevertheless, no differences were noted in COVID-19 severity (p=0.736). No statistically significant differences were identified in overall mortality rate (molnupiravir n=8, 7% vs nirmatrelvir/ritonavir n=7, 6%, p=1.0) or in survival probability (d30 p=0.39, d60 p=0.70, d90 p=0.92, last day of follow up p=0.92). In all patients, deaths were either attributed to COVID-19 or the infection contributed to death. Figure 1. Survival probability of patients treated for COVID-19 with molnupiravir vs nirmatrelvir/ritonavir. a) Day 30 b) Day 60c) Day 90 d) Last day of follow up Summary/Conclusion: In high-risk patients with HM and COVID-19, molnupiravir showed a mortality rate comparable to nirmatrelvir/ritonavir in this matched-pair analysis. Molnupiravir appears to be an alternative for COVID-19 treatment. Keywords: Treatment, Hematological malignancy, Treatment-related mortality, COVID-19