Efficacy of Preexposure Prophylaxis with Monoclonal Antibody Tixagevimab-Cilgavimab against Emerging SARS-CoV-2 Resistant Variants in Patients with Chronic Lymphocytic Leukemia

Introduction: Preexposure prophylaxis with monoclonal antibodies (mAbs) was developed in addition to COVID-19 vaccine for immunocompromised and those with insufficient immune response, among them patients with CLL. Omicron variant and its sublineages evolved mutations that escape mAbs neutralizing effect, yet the extent of which was not studied. Methods: We evaluated anti-spike titers and neutralization activity of COVID-19 wild-type (WT), Delta, Omicron, BA.2, BA.4, and BA.5 before and after tixagevimabcilgavimab (TGM/CGM) dose of 150/150 mg or 300/300 mg in patients with CLL. Results: 70 patients were tested 2 weeks before and 4 weeks after receiving TGM/CGM mAbs. After TGM/CGM, anti-spike ab level increased 170-folds from 13.6 binding antibody unit (BAU)/mL (IQR, 0.4-288) to 2,328 BAU/mL (IQR, 1,681-3,500). Neutralization activity increased in all variants and was 176-folds higher in WT and 55-folds higher in Delta compared to 10-folds higher in Omicron and its sublineages (BA.2 ×11, BA.4 ×4, BA.5 ×18). Over follow-up period of 3 months, 20 patients (29%) with CLL acquired COVID-19 infection, all recovered uneventfully. In a multivariate analysis, anti-spike antibody titer was found a significant predictor for post-TGM/CGM COVID-19 infection. Conclusion: Efficacy of preexposure prophylaxis with TGM/CGM in patients with CLL is significantly reduced in era of Omicron and its sublineages BA.2, BA.4, and BA.5.