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

Abstract

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).

Keywords: COVID-19; Haematology; Malignancy; Nirmatrelvir; SARS-CoV-2.

Fig. 1

Geographical distribution of patients documented in 2022 in EPICOVIDEHA according to the treatment received for COVID-19. A) Overall sample. This figure includes patients from institutions worldwide. Countries with patterns of more than one colour indicate that more than one type of treatment has been administered in the respective country. Blue indicates patients with nirmatrelvir/ritonavir ± other treatments: Italy (n = 59), Spain (n = 31), Belgium (n = 13), Germany (n = 7), France (n = 5), and Austria and Serbia (n = 1, each). Orange indicates patients with other SARS-CoV-2-directed drugs ± other treatments: Italy (n = 284), Spain (n = 162), Denmark (n = 73), Netherlands (n = 59), Germany (n = 51), Croatia (n = 36), Egypt (n = 33), Hungary (n = 32), Austria (n = 31); Belgium and France (n = 29, each), North Macedonia (n = 23), Serbia (n = 20), Czech Republic (n = 19), Greece (n = 18), Argentina, Poland, and Portugal (n = 16, each), Switzerland (n = 13), United Kingdom (n = 11), Sweden (n = 8), Turkey (n = 7), Brazil and Saudi Arabia (n = 6, each), and Bangladesh, Chile, and Hong Kong SAR (n = 1, each). Brown indicates patients with non-SARS-CoV-2-directed drugs: Spain (n = 192), Italy (n = 166), Netherlands (n = 105), Portugal (n = 80), Belgium (n = 35), Croatia (n = 26), France (n = 23), Argentina (n = 20), Austria (n = 15), Egypt (n = 14), Hungary (n = 11), Germany (n = 10), North Macedonia (n = 9), Switzerland (n = 7), Brazil (n = 6), Greece (n = 5), Turkey (n = 4), Serbia (n = 3), Denmark, Poland, and Sweden (n = 2, each), and Czech Republic, Saudi Arabia, Singapore, and United Kingdom (n = 1, each). B) Proportional ambulatory administration of nirmatrelvir/ritonavir. This figure includes patients from European institutions. The darker the blue, the higher proportion of patients receiving ambulatory nirmatrelvir/ritonavir: France (5/5) 100.0%, Italy (48/59) 81.4%, Spain (5/29) 17.2%, Belgium (1/13) 7.7%, and Austria (0/1), Germany (0/7), and Serbia (0/1) 0.0%, each.

Fig. 2

Survival probability by COVID-19 treatment strategy. A) Summarised treatment strategies. This table includes patients from European institutions. B) Detailed treatment strategies. This table includes patients from European institutions.