SARS-COV-2 Pre-Exposure Prophylaxis With Tixagevimab-Cilgavimab in Haematological, Immunocompromised Patients in the Omicron Era.

Abstract

Background: Pre-exposure prophylaxis with tixagevimab-cilgavimab significantly reduced severe COVID-19 outcomes in high-risk individuals during the pre-Omicron era (PROVENT trial). However, efficacy in patients with haematological malignancies (HM) was underreported. The rapid emergence of Omicron strains in 2021 showed reduced neutralizing activity in preclinical data, but real-world data remains limited due to short follow-up.

Patients and methods: We aimed to evaluate the effectiveness and safety of tixagevimab-cilgavimab in 86 HM patients during the early Omicron wave, including the BA.2, BA.5, and XBB.1 sublineages. These patients received PrEP between February and August 2022 due to impaired vaccine response (72%) and B-cell depletion (46.5%). They were followed prospectively until April 2023, with a median follow-up of 297 days.

Results: Breakthrough SARS-CoV-2 infections occurred in 32.6% of patients, with 22.1% within six months. Infections within six months were milder and shorter. B-cell depletion within six (p = 0.035) and twelve months (p = 0.016) was identified as risk factor for breakthrough infections. No new safety events were reported.

Conclusion: Our data showed that tixagevimab-cilgavimab prophylaxis effectively reduces severe COVID-19 outcomes in patients with HM, particularly within the first six months, even during the Omicron era. However, those with recent B-cell depletion (within 12 months) remained at high risk.