Despite lower virulence, the omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) still poses a relevant threat for immunocompromised patients. A retrospective multicentric study was conducted to evaluate the efficacy of pre-exposure prophylaxis with tixagevimab/cilgavimab (Evusheld) with a 6-month follow-up for preventing severe COVID-19 in adult patients with hematology malignancy. Among the 606 patients in the cohort, 96 (16%) contracted COVID-19 with a median of 98.5 days after Evusheld administration. A total of 75% of patients had asymptomatic or mild severity of COVID-19, while just 25% of patients with SARS-CoV-2 positivity had to be hospitalized. Two patients (2%) died directly, and one patient (1%) in association with COVID-19. Eight patients (1.3%) of every cohort experienced adverse events related to Evusheld, mostly grade 1 and of reversible character. It was found that complete vaccination status or positive seroconversion was not associated with lower risk of COVID-19 infection. Previous treatment with an anti-CD20 monoclonal antibody was associated with higher rates of COVID-19, while previous treatment with anti-CD38 monoclonal antibody was not, as was the case for recipients of hematopoietic stem cell transplantation or CAR-T cell therapy. Presence of other comorbidities was not associated with more severe COVID-19. The results support the growing evidence for Evusheld's efficacy against severe COVID-19 in patients with hematology malignancies.

4th Department of Internal Medicine Haematology Hospital and Faculty of Medicine Charles University Hradec Kralove Czech Republic

Department of Haemato Oncology Faculty of Medicine and Dentistry Palacky University and University Hospital Olomouc Olomouc Czech Republic

Department of Haematology and Oncology University Hospital Pilsen Pilsen Czech Republic

Department of Haematooncology University Hospital Ostrava 17 Listopadu 1790 5 708 52 Ostrava Czech Republic

Department of Histology and Embryology Faculty of Medicine Pilsen Czech Republic

Department of Internal Medicine and Haematology Faculty Hospital Kralovske Vinohrady Prague Czech Republic

Department of Social and Clinical Pharmacy Faculty of Pharmacy in Hradec Kralove Charles University Hradec Kralove Czech Republic

Faculty of Medicine University of Ostrava Ostrava Czech Republic

Hospital Pharmacy University Hospital Hradec Kralove Hradec Kralove Czech Republic

Institute of Haematology and Blood Transfusion Prague Czech Republic

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Levin MJ, Ustianowski A, De Wit S, Launay O, Avila M, Templeton A, et al. Intramuscular AZD7442 (tixagevimab–cilgavimab) for prevention of COVID-19. N Engl J Med. 2022;386(23):2188–2200. doi: 10.1056/NEJMoa2116620. PubMed DOI PMC

Montgomery H, Hobbs FDR, Padilla F, Arbetter D, Templeton A, Seegobin S, et al. Efficacy and safety of intramuscular administration of tixagevimab–cilgavimab for early outpatient treatment of COVID-19 (TACKLE): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2022;10(10):985–996. doi: 10.1016/S2213-2600(22)00180-1. PubMed DOI PMC

Gandhi RT, Lynch JB, Del Rio C. Mild or moderate COVID-19. N Engl J Med. 2020;383(18):1757–1766. doi: 10.1056/NEJMcp2009249. PubMed DOI

Šušol O, Hájková B, Zelená H, Hájek R. Third dose of COVID-19 vaccine restores immune response in patients with haematological malignancies after loss of protective antibody titres. Br J Haematol. 2022;197(3):302–305. doi: 10.1111/bjh.18073. PubMed DOI

Ocon AJ, Ocon KE, Battaglia J, Low SK, Neupane N, Saeed H, et al. Real-world effectiveness of tixagevimab and cilgavimab (Evusheld) in patients with hematological malignancies. J Hematol. 2022;11(6):210–215. doi: 10.14740/jh1062. PubMed DOI PMC

Nyberg T, Ferguson NM, Nash SG, Webster HH, Flaxman S, Andrews N, et al. Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study. Lancet. 2022;399(10332):1303–12. doi: 10.1016/S0140-6736(22)00462-7. PubMed DOI PMC

Blennow O, Salmanton-García J, Nowak P, Itri F, Van Doesum J, López-García A, et al. Outcome of infection with omicron SARS-CoV-2 variant in patients with hematological malignancies: an EPICOVIDEHA survey report. Am J Hematol. 2022;97(8):E312–E317. doi: 10.1002/ajh.26626. PubMed DOI PMC

Marchesi F, Salmanton-García J, Buquicchio C, Itri F, Besson C, Dávila-Valls J, et al. Passive pre-exposure immunization by tixagevimab/cilgavimab in patients with hematological malignancy and COVID-19: matched-paired analysis in the EPICOVIDEHA registry. J Hematol OncolJ Hematol Oncol. 2023;16(1):32. doi: 10.1186/s13045-023-01423-7. PubMed DOI PMC

Jondreville L, D’Aveni M, Labussière-Wallet H, Le Bourgeois A, Villate A, Berceanu A, et al. Pre-exposure prophylaxis with tixagevimab/cilgavimab (AZD7442) prevents severe SARS-CoV-2 infection in recipients of allogeneic hematopoietic stem cell transplantation during the Omicron wave: a multicentric retrospective study of SFGM-TC. J Hematol OncolJ Hematol Oncol. 2022;15(1):169. doi: 10.1186/s13045-022-01387-0. PubMed DOI PMC

La J, Wu JTY, Branch-Elliman W, Huhmann L, Han SS, Brophy M, et al. Increased COVID-19 breakthrough infection risk in patients with plasma cell disorders. Blood. 2022;140(7):782–785. doi: 10.1182/blood.2022016317. PubMed DOI PMC

Terpos E, Gavriatopoulou M, Ntanasis-Stathopoulos I, Briasoulis A, Gumeni S, Malandrakis P, et al. The neutralizing antibody response post COVID-19 vaccination in patients with myeloma is highly dependent on the type of anti-myeloma treatment. Blood Cancer J. 2021;11(8):1–9. doi: 10.1038/s41408-021-00530-3. PubMed DOI PMC

Vijenthira A, Gong IY, Fox TA, Booth S, Cook G, Fattizzo B, et al. Outcomes of patients with hematologic malignancies and COVID-19: a systematic review and meta-analysis of 3377 patients. Blood. 2020;136(25):2881–2892. doi: 10.1182/blood.2020008824. PubMed DOI PMC

Roeker LE, Knorr DA, Thompson MC, Nivar M, Lebowitz S, Peters N, et al. COVID-19 vaccine efficacy in patients with chronic lymphocytic leukemia. Leukemia. 2021;35(9):2703–2705. doi: 10.1038/s41375-021-01270-w. PubMed DOI PMC

Davis JA, Granger K, Roubal K, Smith D, Gaffney KJ, McGann M, et al. Efficacy of tixagevimab-cilgavimab in preventing SARS-CoV-2 for patients with B-cell malignancies. Blood. 2023;141(2):200–203. doi: 10.1182/blood.2022018283. PubMed DOI PMC

Angotzi F, Petrella M, Berno T, Binotto G, Bonetto G, Branca A, et al. (2023) Tixagevimab/cilgavimab as pre-exposure prophylaxis against SARS-CoV-2 in patients with hematological malignancies. Front Oncol 13 PubMed PMC

Andrews N, Stowe J, Kirsebom F, Toffa S, Rickeard T, Gallagher E, et al. Covid-19 vaccine effectiveness against the Omicron (B.1.1.529) variant. N Engl J Med. 2022;386(16):1532–46. doi: 10.1056/NEJMoa2119451. PubMed DOI PMC

Lau JJ, Cheng SMS, Leung K, Lee CK, Hachim A, Tsang LCH, et al. Real-world COVID-19 vaccine effectiveness against the Omicron BA.2 variant in a SARS-CoV-2 infection-naive population. Nat Med. 2023;29(2):348–57. doi: 10.1038/s41591-023-02219-5. PubMed DOI PMC

Underlying medical conditions associated with higher risk for severe COVID-19: information for healthcare professionals [Internet]. 2020. CDC. Available from: https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html

Kamboj M, Laracy JC, Usiak S, Babady NE, Yan J, Seo SK (2023) Outcomes of hematologic malignancy patients with SARS-CoV-2 breakthrough infections after tixagevimab-cilgavimab during community transmission of monoclonal antibody resistant variants. J Infect 0(0) PubMed

Cao Y, Yisimayi A, Jian F, Song W, Xiao T, Wang L, et al. BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection. Nature. 2022;608(7923):593–602. doi: 10.1038/s41586-022-04980-y. PubMed DOI PMC

Ke H, Chang MR, Marasco WA. Immune evasion of SARS-CoV-2 Omicron subvariants. Vaccines. 2022;10(9):1545. doi: 10.3390/vaccines10091545. PubMed DOI PMC

Ao D, He X, Hong W, Wei X. The rapid rise of SARS-CoV-2 Omicron subvariants with immune evasion properties: XBB.1.5 and BQ.1.1 subvariants. MedComm. 2023;4(2):e239. doi: 10.1002/mco2.239. PubMed DOI PMC

Wang Q, Iketani S, Li Z, Liu L, Guo Y, Huang Y, et al. Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants. Cell. 2023;186(2):279–286.e8. doi: 10.1016/j.cell.2022.12.018. PubMed DOI PMC

Planas D, Bruel T, Staropoli I, Guivel-Benhassine F, Porrot F, Maes P, et al. Resistance of Omicron subvariants BA.2.75.2, BA.4.6, and BQ.1.1 to neutralizing antibodies. Nat Commun. 2023;14(1):824. doi: 10.1038/s41467-023-36561-6. PubMed DOI PMC

Cao Y, Jian F, Wang J, Yu Y, Song W, Yisimayi A, et al. Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution. Nature. 2023;614(7948):521–529. PubMed PMC

Yue C, Song W, Wang L, Jian F, Chen X, Gao F, et al. (2023) Enhanced transmissibility of XBB.1.5 is contributed by both strong ACE2 binding and antibody evasion. bioRxiv; 2023.01.03.522427 PubMed PMC

Zhao Q, Wang X, Zhang Z, Liu X, Wang P, Cao J, et al. Serum neutralization of SARS-CoV-2 Omicron BA.2, BA2.75, BA.2.76, BA.5, BF.7, BQ.1.1 and XBB.1.5 in individuals receiving Evusheld. J Med Virol. 2023;95(7):e28932. doi: 10.1002/jmv.28932. PubMed DOI

FDA announces Evusheld is not currently authorized for emergency use in the U.S. [Internet]. FDA; 2023. FDA. Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-announces-evusheld-not-currently-authorized-emergency-use-us