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

    Ohad Benjamini,Tamar Tadmor,Abraham Avigdor,Rotem Gershon,Limor Kliker, Florin Fares,Nofar Atari, Ilana Laevsky,Bayan Abdelkader,Tammy Hod,Orit Golan-Shany,Michal Mandelboim,Galia Rahav

    Acta haematologica（2024）

    Chaim Sheba Med Ctr | Bnai Zion Med Ctr | Tel Aviv Univ | Minist Hlth | Sheba Med Ctr

    Cited 1|Views15
    Abstract
    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 tixagevimab-cilgavimab (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 x11, BA.4 x4, BA.5 x18). 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.
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    Chronic lymphocytic leukemia,CLL,COVID-19,Tixagevimab-cilgavimab,Preexposure prophylaxis,COVID-19 variants
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    【要点】：研究评估了使用单克隆抗体Tixagevimab-Cilgavimab对慢性淋巴细胞白血病（CLL）患者预防SARS-CoV-2新变种的效果，发现对于Omicron及其子变种BA.2、BA.4和BA.5的预防效果显著降低。
    

    【方法】：通过检测CLL患者在接受150/150 mg或300/300 mg TGM/CGM单抗前后对COVID-19野生型、Delta、Omicron及其子变种BA.2、BA.4和BA.5的抗体滴度和中和活性。
    

    【实验】：在70名CLL患者中进行了实验，他们在接受TGM/CGM单抗前后的2周和4周进行了测试，结果发现抗体水平显著增加，对Omicron及其子变种的中和活性提升幅度不如对野生型和Delta变种，在3个月的随访期间，29%的患者感染了COVID-19，但均顺利恢复，研究显示抗体的滴度是感染COVID-19的显著预测因子。