Incidence of breakthrough COVID-19 in patients with hematological disorders who received pre-exposure prophylaxis with tixagevimab-cilgavimab: a retrospective study in Japan - Report - MDSpire
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Incidence of breakthrough COVID-19 in patients with hematological disorders who received pre-exposure prophylaxis with tixagevimab-cilgavimab: a retrospective study in Japan
Breakthrough COVID-19 in Hematological Patients Receiving Tixagevimab-Cilgavimab in Japan
Overview
In a retrospective study of 257 hematological disorder patients in Japan receiving 300 mg doses of Tixagevimab-Cilgavimab (Tix/Cil) for COVID-19 pre-exposure prophylaxis, 7.5% experienced breakthrough infections. Despite breakthrough cases, no COVID-19-related deaths occurred, and severe disease progression was prevented with early antiviral treatment.
Background
SARS-CoV-2 has caused a global pandemic with evolving variants impacting infection dynamics. Immunocompromised patients, such as those with hematological disorders, often have suboptimal vaccine responses and remain at high risk for severe COVID-19. Tixagevimab/cilgavimab, a neutralizing antibody combination targeting the spike protein, has been used as pre-exposure prophylaxis in immunosuppressed populations. Real-world data on breakthrough infections in this group, especially in Japan, remain limited.
Data Highlights
Characteristic
Value
Number of patients
257
Median age (range)
60 years (21–89)
Male patients
148 (58%)
Median follow-up
73 days (IQR 49.75–91)
Patients post-HSCT
148 (61% within 1 year of Tix/Cil)
Received anti-CD20 antibody within 1 year
60 (23.3%)
Received CAR-T therapy within 1 year
11 (9.3%)
Received ≥3 vaccine doses
141 (51%)
Breakthrough COVID-19 cases
18 (7.5%)
Cumulative infection rate at 30 days
4.3%
Cumulative infection rate at 100 days
8.2%
COVID-19 severity among infected
Asymptomatic: 1; Mild: 11; Moderate: 2; Severe: 4
Hospitalized patients
12 (67% of infected)
Median time to COVID-19 onset post-Tix/Cil
25 days (range 1–93)
COVID-19 mortality
0
Key Findings
Breakthrough COVID-19 occurred in 7.5% of hematological patients receiving 300 mg Tix/Cil prophylaxis.
Majority of breakthrough cases were mild or moderate; no deaths were reported.
Hospitalization was common (67% of infected), reflecting cautious management of high-risk patients.
Median time to breakthrough infection was 25 days post-Tix/Cil administration, with some cases occurring within 14 days.
No significant associations were found between breakthrough infection and age, sex, vaccination status, HSCT, or anti-CD20 therapy in univariate analysis.
The dominant circulating variant during the study was Omicron BA.5, which may reduce Tix/Cil neutralization efficacy.
Clinical Implications
Tixagevimab/cilgavimab at 300 mg doses provides partial protection against COVID-19 breakthrough infections in immunocompromised hematological patients, with preserved efficacy in preventing severe disease and mortality. Clinicians should maintain vigilant monitoring and early antiviral treatment for breakthrough cases, especially within the first month post-prophylaxis. Consideration of circulating variants and patient risk factors remains important in managing prophylaxis strategies.
Conclusion
This study provides valuable real-world evidence from Japan demonstrating that Tix/Cil pre-exposure prophylaxis reduces severe COVID-19 outcomes in hematological patients despite breakthrough infections. Continued surveillance and tailored management are essential to optimize protection in this vulnerable population.
References
SARS-CoV-2 Emergence and Spread, 2019
Vaccination and Immune Response in Hematological Disorders, 2022
Tixagevimab/Cilgavimab Efficacy Studies, 2022
Breakthrough COVID-19 in Immunocompromised Patients, 2023
Japanese Ministry of Health Guidance on Tix/Cil, 2022
