Impact of Sars-CoV-2 Prophylaxis with Tixagevimab-Cilgavimab in High-Risk Patients with B-Cell Malignancies: A Single-Center Retrospective Study

Severe Acute Respiratory Syndrome CoronaVirus‐2 (SARS‐CoV‐2) infection can result in different clinical manifestations (COVID-19), from asymptomatic disease to life-threatening respiratory insufficiency.1 Onco-hematologic patients are at higher risk of developing severe COVID-19.2 In particular, patients affected by lymphoproliferative diseases, given the impaired cell-mediated and antibody-mediated immunity and treatment toxicity, more often develop a symptomatic and more serious COVID-19 disease.2-3 Various prophylactic and therapeutic strategies are used against COVID‐19, such as vaccines, antiviral drugs, and S‐protein monoclonal antibodies (anti‐S MoAbs). The efficacy of antiviral strategies often proved to be dependent on SARS-CoV-2 variants.4-6 Pre-exposure prophylaxis with AZD442/Evusheld (tixagevimab-cilgavimab) may be a complementary strategy to decrease the incidence or severity of COVID-19 for patients with hematologic malignancies. Tixagevimab-cilgavimab is a combination of two monoclonal antibodies (T-C MoAb) that bind SARS-CoV-2 spike protein and inhibit the attachment to the surface of cells, preventing viral entry in the cell and COVID-19 development.7,8 In the PROVENT trial, a phase 3 study, 5197 patients were randomized to receive T-C MoAB or placebo, reporting a favorable incidence of only 0.2% of symptomatic COVID-19 in the T-C MoAb arm, even if it included only 3.3% of cancer patients receiving T-C MoAb and was conducted before the Omicron era.8 Based on these findings, T-C MoAB was approved by the Agenzia Italiana del Farmaco (AIFA) as pre-exposure prophylaxis for patients at high risk of severe COVID-19; therefore, it was regularly employed at our institution.9 However, recent studies, mainly performed in vitro, suggested inferior efficacy against omicron variants.10-12 Our aim was to evaluate if this strategy's upcoming reported clinical benefit and safety to patients with hematologic malignancies were still in force in a real-life setting of high-risk hematologic patients during the omicron-predominant COVID-19 wave in Italy