Impact of SARS-CoV-2 infection on bispecific antibody treatment in patients with B-cell lymphoproliferative disorders

Abstract

Despite advances in vaccination and the use of antiviral treatments, patients with hematologic malignancies, including B-cell lymphoproliferative disorders, are particularly vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The recent introduction of bispecific antibodies (BsAbs) in the treatment algorithm of relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL) has raised concerns regarding their impact on COVID-19 outcomes. This study aimed to evaluate the impact of SARS-CoV-2 infection on treatment outcomes in patients receiving BsAbs. We assessed the severity of COVID-19 and SARS-CoV-2 serostatus, with antibody titers measured before, during, and after BsAbs administration. A total of 109 patients with B-NHL treated with BsAbs from March 2020 to January 2023 were included. SARS-CoV-2 infection was observed in 56 patients (51%), with 36% experiencing prolonged viral shedding, causing therapy delays in 78% of patients and permanent discontinuations in 19%. Regarding COVID-19 severity, 36% of patients presented moderate, 20% severe, and 12% critical disease. Seven patients (13%) died owing to COVID-19 pneumonia. Similar to observations with anti-CD20 monoclonal antibodies, BsAbs were associated with negative antispike serostatus for at least 6 months after treatment completion. Importantly, this lack of seroconversion was linked with severe disease and increased mortality. These findings underscore important considerations for the management of patients receiving BsAbs.