Hoechstetter Manuela A, Hollwich Eva-Maria, Illner Doris, Pham Thu-Trang, von Bergwelt-Baildon Michael, Dreyling Martin, Wendtner Clemens-Martin
Department of Haematology, Oncology, Immunology, Palliative Medicine, Infectious Diseases and Tropical Medicine, Muenchen Klinik Schwabing, Munich, Germany.
Department of Medicine III and Comprehensive Cancer Center (CCC Munich LMU), LMU University Hospital, Ludwig-Maximilians University, Munich, Germany.
Eur J Haematol. 2025 Apr;114(4):690-699. doi: 10.1111/ejh.14377. Epub 2025 Jan 6.
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.
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.
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.
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.
在奥密克戎毒株出现之前的时期，替沙格韦单抗-西加韦单抗暴露前预防显著降低了高危人群中重症新冠病毒感染2019（COVID-19）的发生率（PROVENT试验）。然而，血液系统恶性肿瘤（HM）患者的疗效报告不足。2021年奥密克戎毒株的迅速出现显示临床前数据中的中和活性降低，但由于随访时间短，真实世界数据仍然有限。
我们旨在评估替沙格韦单抗-西加韦单抗在奥密克戎毒株早期流行期间对86例HM患者的有效性和安全性，包括BA.2、BA.5和XBB.1亚谱系。由于疫苗反应受损（72%）和B细胞耗竭（46.5%），这些患者在2022年2月至8月期间接受了暴露前预防。对他们进行前瞻性随访至2023年4月，中位随访时间为297天。
32.6%的患者发生了突破性严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染，其中22.1%发生在六个月内。六个月内的感染症状较轻，病程较短。六个月（p = 0.035）和十二个月（p = 0.016）内的B细胞耗竭被确定为突破性感染的危险因素。未报告新的安全事件。
我们的数据表明，替沙格韦单抗-西加韦单抗预防可有效降低HM患者中重症COVID-19的发生率，尤其是在头六个月内，即使在奥密克戎毒株流行期间也是如此。然而，近期有B细胞耗竭（12个月内）的患者仍然处于高风险中。
