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Efficacy and safety of tixagevimab/cilgavimab as passive immunisation against COVID-19 infections in patients with hematological malignancies

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Abstract

Monoclonal antibodies, as tixagevimab/cilgavimab, have been introduced as prophylaxis against COVID-19 infections in high-risk populations. However, data on efficacy are limited. This study investigates efficacy and tolerability of tixagevimab/cilgavimab in hematological patients under real-life conditions. Tixagevimab/cilgavimab was administered to 155 hematological patients (March-August 2022) at two Austrian centres. S/RBD-antibody assessments were performed before (T0), four weeks (T1), and six months (T2) after application. Side effects, the occurrence of COVID-19 infections, and the course of S/RBD-antibody titres were analysed retrospectively in relation to clinical variables. 155 hematological patients, who refused tixagevimab/cilgavimab, were included as a control group to compare the frequency of COVID-19 infections. Of all immunised patients (52.3% males; 91% triple vaccinated), 25.8% had a COVID-19 breakthrough infection (76% mild) compared to 43.9% in the control group. Patients with chronic lymphocytic leukaemia (CLL)/lymphoma were at highest risk of a COVID-19 infection (OR = 2.21; 95% CI 1.05–4.65; p = 0.037). After immunisation, a steep increase in median antibody levels (1193.4BAU/ml, IQR 0–2318.94) was observed in 67.8%, followed by a rapid decrease between T1 and T2 (465.95BAU/ml, IQR 0–1900.65.3) with the greatest declines in CLL/lymphoma (848.7BAU/ml, IQR 0–1949.6, p = 0.026). Side-effects occurred in 21.2% (CTCAE I/II). These real-world data indicate that S/RBD antibodies respond rapidly after passive immunisation in all hematological patients without safety concerns. Given the rapid decline in S/RBD antibodies, early booster immunisations should be considered for future scenarios in this vulnerable group.

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Authors and Affiliations

  1. Department of Internal Medicine II, Academic Teaching Hospital Feldkirch, Carinagasse 47, 6800, Feldkirch, Austria

    Patrick Reimann, Bernd Hartmann, Luciano Severgnini, Alex Winkler, Theresia Lang, Minh Huynh, Klaus Gasser, Julia Rüger, Michele Atzl, Thomas Winder & Magdalena Anna Benda

  2. Private University of the Principality of Liechtenstein, Triesen, Principality of Liechtenstein

    Patrick Reimann, Luciano Severgnini, Sylvia Mink & Magdalena Anna Benda

  3. Innsbruck University Hospital, Internal Medicine V: Haematology & Oncology, Innsbruck, Austria

    Verena Petzer, Stefan Schmidt, Normann Steiner, Eberhard Gunsilius, David Nachbaur, Wolfgang Willenbacher & Dominik Wolf

  4. Molecular Biology Laboratory, Vorarlberg Institute for Vascular Investigation and Treatment, Dornbirn, Austria

    Axel Mündlein

  5. Medical Central Laboratories, Feldkirch, Austria

    Sylvia Mink & Peter Fraunberger

  6. Central Institute for Med. and Chem. Laboratory Diagnostics (ZIMCL) With Interdisciplinary Hematological Competence Centre (IHK), Medical University Innsbruck, Innsbruck, Austria

    Andrea Griesmacher

  7. Syndena,GmbH Connect to Cure, Innsbruck, Austria

    Wolfgang Willenbacher

  8. University of Zurich, Zurich, Switzerland

    Thomas Winder

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  1. Patrick Reimann
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Contributions

All authors of this research paper have directly participated in the planning, execution, or analysis of the study.

MB, PR, BH and TW contributed to the study conception and design. MB, PR, VP, AM, BH, LS, AW, TL, MH, KG, JR, MA, SM, PF, SS, NS, AG, EG, DN, WW, DW and TW performed data collection and analysis. MB and PR wrote the first draft of the manuscript, and all authors commented on previous versions. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Magdalena Anna Benda.

Ethics declarations

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the Medical University of Innsbruck (EC No: 1088/2021 and 1355/2022).

Competing interests

The authors declare no competing interests.

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Patrick Reimann and Verena Petzer contributed equally to this work as co-first authors.

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Reimann, P., Petzer, V., Mündlein, A. et al. Efficacy and safety of tixagevimab/cilgavimab as passive immunisation against COVID-19 infections in patients with hematological malignancies. Ann Hematol (2024). https://doi.org/10.1007/s00277-024-05671-6

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