Molnupiravir and nirmatrelvir/ritonavir are antivirals used to prevent severe SARS-CoV-2 infections, reducing hospitalization and mortality rates. Nirmatrelvir/ritonavir was authorised in Europe in December 2021. Despite molnupiravir may be an alternative to nirmatrelvir/ritonavir, because it displays less frequent drug-drug interactions and contraindications, it is not yet licensed. Little is known about comparative efficacy of the two drugs in patients with haematological malignancy (HM) at high-risk of severe COVID-19. Thus, we assess the effectiveness of molnupiravir compared to nirmatrelvir/ritonavir in our HM patient cohort.
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 (±10 years), baseline HM severity and hospital admission to controls treated with nirmatrelvir/ritonavir.
A total of 115 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, 69 (60%) patients were male; with a median age of 64 years (IQR 53-74) for molnupiravir recipients and 64 years (IQR 54-73) for nirmatrelvir/ritonavir recipients. 57% (n=66) of the patients had controlled baseline HM, 13% (n=15) stable, and 30% (n=34) active disease at COVID-19 onset in each of the groups. 33% (n=38, each) of patients were admitted to hospital during their COVID-19 episode. Although a similar proportion of vaccinated patients was observed in both groups (molnupiravir n=77, 67% vs nirmatrelvir/ritonavir n=82, 71%), those under nirmatrelvir/ritonavir more often had received four doses (n=21, 18%) as compared to the ones under molnupiravir (n=5, 4%, p<0.001). Nevertheless, no differences were noted in COVID-19-episode severity (p=0.63). No statistically significant differences were identified in overall mortality rate (n=8, 7% for both treatments, p=1.0) or in survival probability (d30 p=0.4, d60 p=0.95, d90 p=0.89, last day of follow up p=0.89). In all patients, deaths were either attributed to COVID-19 or the infection contributed to death.
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 to nirmatrelvir/ritonavir for COVID-19 treatment in haematological malignancy patients.