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

Overview

Journal Acta Haematol

Specialty Hematology

Date 2024 Mar 12

PMID 38471491

Authors

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

Affiliations

Soon will be listed here.

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 ×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.

Citing Articles

COVID-19 in Patients with Chronic Lymphocytic Leukemia: What Have We Learned?.

Harel R, Itchaki G Acta Haematol. 2023; 147(1):60-72.

PMID: 37820599 PMC: 11251671. DOI: 10.1159/000534540.

References

Bertrand D, Laurent C, Lemee V, Lebourg L, Hanoy M, Le Roy F . Efficacy of Tixagevimab/Cilgavimab Prophylaxis and Vaccination on Omicron Variants (BA.1, BA.2, BA.5, and BQ.1.1) in Kidney Transplant Recipients. Clin J Am Soc Nephrol. 2023; 18(10):1343-1345. PMC: 10578625. DOI: 10.2215/CJN.0000000000000241. View

Tuekprakhon A, Nutalai R, Dijokaite-Guraliuc A, Zhou D, Ginn H, Selvaraj M . Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum. Cell. 2022; 185(14):2422-2433.e13. PMC: 9181312. DOI: 10.1016/j.cell.2022.06.005. View

Bruel T, Stefic K, Nguyen Y, Toniutti D, Staropoli I, Porrot F . Longitudinal analysis of serum neutralization of SARS-CoV-2 Omicron BA.2, BA.4, and BA.5 in patients receiving monoclonal antibodies. Cell Rep Med. 2022; 3(12):100850. PMC: 9706550. DOI: 10.1016/j.xcrm.2022.100850. View

Mato A, Roeker L, Lamanna N, Allan J, Leslie L, Pagel J . Outcomes of COVID-19 in patients with CLL: a multicenter international experience. Blood. 2020; 136(10):1134-1143. PMC: 7472711. DOI: 10.1182/blood.2020006965. View

Roeker L, Eyre T, Thompson M, Lamanna N, Coltoff A, Davids M . COVID-19 in patients with CLL: improved survival outcomes and update on management strategies. Blood. 2021; 138(18):1768-1773. PMC: 8313815. DOI: 10.1182/blood.2021011841. View

Sheward D, Kim C, Ehling R, Pankow A, Dopico X, Dyrdak R . Neutralisation sensitivity of the SARS-CoV-2 omicron (B.1.1.529) variant: a cross-sectional study. Lancet Infect Dis. 2022; 22(6):813-820. PMC: 8930016. DOI: 10.1016/S1473-3099(22)00129-3. View

Passamonti F, Cattaneo C, Arcaini L, Bruna R, Cavo M, Merli F . Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study. Lancet Haematol. 2020; 7(10):e737-e745. PMC: 7426107. DOI: 10.1016/S2352-3026(20)30251-9. View

Pagano L, Salmanton-Garcia J, Marchesi F, Busca A, Corradini P, Hoenigl M . COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA). J Hematol Oncol. 2021; 14(1):168. PMC: 8515781. DOI: 10.1186/s13045-021-01177-0. View

Planas D, Saunders N, Maes P, Guivel-Benhassine F, Planchais C, Buchrieser J . Considerable escape of SARS-CoV-2 Omicron to antibody neutralization. Nature. 2022; 602(7898):671-675. DOI: 10.1038/s41586-021-04389-z. View

10.

Al-Obaidi M, Gungor A, Kurtin S, Mathias A, Tanriover B, Zangeneh T . The Prevention of COVID-19 in High-Risk Patients Using Tixagevimab-Cilgavimab (Evusheld): Real-World Experience at a Large Academic Center. Am J Med. 2022; 136(1):96-99. PMC: 9519524. DOI: 10.1016/j.amjmed.2022.08.019. View

11.

Herishanu Y, Rahav G, Levi S, Braester A, Itchaki G, Bairey O . Efficacy of a third BNT162b2 mRNA COVID-19 vaccine dose in patients with CLL who failed standard 2-dose vaccination. Blood. 2021; 139(5):678-685. PMC: 8648353. DOI: 10.1182/blood.2021014085. View

12.

Bertrand D, Laurent C, Lemee V, Lebourg L, Hanoy M, Le Roy F . Efficacy of anti-SARS-CoV-2 monoclonal antibody prophylaxis and vaccination on the Omicron variant of COVID-19 in kidney transplant recipients. Kidney Int. 2022; 102(2):440-442. PMC: 9125992. DOI: 10.1016/j.kint.2022.05.007. View

13.

Al Jurdi A, Morena L, Cote M, Bethea E, Azzi J, Riella L . Tixagevimab/cilgavimab pre-exposure prophylaxis is associated with lower breakthrough infection risk in vaccinated solid organ transplant recipients during the omicron wave. Am J Transplant. 2022; 22(12):3130-3136. PMC: 9906353. DOI: 10.1111/ajt.17128. View

14.

Otiniano A, Van de Wyngaert Z, Brissot E, Dulery R, Gozlan J, Daguenel A . Tixagevimab/cilgavimab for Omicron SARS-CoV-2 infection in patients with haematologic diseases. Bone Marrow Transplant. 2022; 58(3):340-342. PMC: 9734768. DOI: 10.1038/s41409-022-01894-1. View

15.

Suribhatla R, Starkey T, Ionescu M, Pagliuca A, Richter A, Lee L . Systematic review and meta-analysis of the clinical effectiveness of tixagevimab/cilgavimab for prophylaxis of COVID-19 in immunocompromised patients. Br J Haematol. 2023; 201(5):813-823. DOI: 10.1111/bjh.18782. View

16.

Arora P, Kempf A, Nehlmeier I, Schulz S, Jack H, Pohlmann S . Omicron sublineage BQ.1.1 resistance to monoclonal antibodies. Lancet Infect Dis. 2022; 23(1):22-23. PMC: 9707647. DOI: 10.1016/S1473-3099(22)00733-2. View

17.

Ryu D, Kang B, Noh H, Woo S, Lee M, Nuijten P . The in vitro and in vivo efficacy of CT-P59 against Gamma, Delta and its associated variants of SARS-CoV-2. Biochem Biophys Res Commun. 2021; 578:91-96. PMC: 8436435. DOI: 10.1016/j.bbrc.2021.09.023. View

18.

Imai M, Ito M, Kiso M, Yamayoshi S, Uraki R, Fukushi S . Efficacy of Antiviral Agents against Omicron Subvariants BQ.1.1 and XBB. N Engl J Med. 2022; 388(1):89-91. PMC: 9749618. DOI: 10.1056/NEJMc2214302. View

19.

Davis J, Granger K, Roubal K, Smith D, Gaffney K, McGann M . Efficacy of tixagevimab-cilgavimab in preventing SARS-CoV-2 for patients with B-cell malignancies. Blood. 2022; 141(2):200-203. PMC: 9636601. DOI: 10.1182/blood.2022018283. View

20.

Chatzikonstantinou T, Kapetanakis A, Scarfo L, Karakatsoulis G, Allsup D, Cabrero A . COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study. Leukemia. 2021; 35(12):3444-3454. PMC: 8559135. DOI: 10.1038/s41375-021-01450-8. View