Predictors of SARS-CoV-2 Omicron breakthrough infection after receipt of AZD7442 (tixagevimab-cilgavimab) for pre-exposure prophylaxis among hematologic malignancy patients

Abstract

AZD7442 (tixagevimab-cilgavimab) is a combination of two human monoclonal antibodies for preexposure prophylaxis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among highrisk patients who do not mount a reliable vaccine response. Foremost among these are hematologic malignancy patients with limited clinical trial or real-world experience to assess the effectiveness of this combination treatment since the emergence of Omicron and its subvariants. We performed a retrospective study of 892 highrisk hematologic malignancy patients who received AZD7442 at Memorial Sloan Kettering Cancer Center in New York City from January 1, 2022 to July 31, 2022. We evaluated demographic, clinical, and laboratory characteristics and performed regression analyses to evaluate risk factors for breakthrough infection. We also evaluated the impact of updated AZD7442 dosing regimens on the risk of breakthrough infection. Among 892 patients, 98 (10.9%) had a breakthrough infection during the study period. A majority received early outpatient treatment (82%) and eventually eight (8.2%) required hospitalization for management of Coronavirus Disease 2019 (COVID-19), with a single instance of severe COVID-19 and death. Patients who received a repeat dose or a higher first-time dose of AZD7442 had a lower incidence of breakthrough infection. Univariate analyses did not reveal any significant predictors of breakthrough infection. While AZD7442 is effective at reducing SARS-CoV-2 breakthrough infection in patients with hematologic malignancies, no risk factors reliably predicted risk of infection. Patients who received updated dosing regimens as per Food and Drug Administration guidelines had better protection against breakthrough infection.

Efficacy and safety of tixagevimab‐cilgavimab versus SARS‐CoV‐2 breakthrough infection in the hematological conditions

“…These results confirm what is found in different studies (Table 3), 24,25 with the strength of being based on a larger cohort of patients managed uniformly, with longer follow-up, thus showing what baseline factors are associated with higher risk and comparing different infection duration before and after prophylaxis. Regarding the symptomatic breakthrough infection shown in the PROVENT trial (11% at the data cutoff), our cohort experienced a significantly higher occurrence.…”

Prolonged Viral Shedding in Cancer Patients with Asymptomatic or Mild Omicron Infection: A Retrospective Study

“… 24 , 28 Laracy’s study suggested that AZD7442 had positive protective effect on Omicron in patients with hematological malignancies, and the protective effect may be related to repeated administration or higher first dose. 29 Evidence of solid tumors is lacking. Although the benefit may be lower, AZD7442 is currently the only available pre-exposure prophylaxis.…”

Improving the safety of CAR‐T‐cell therapy: The risk and prevention of viral infection for patients with relapsed or refractory B‐cell lymphoma undergoing CAR‐T‐cell therapy

“…131,132 As demonstrated, it may reduce the risk of severe infection and death in patients with breakthrough infections. 131,[133][134][135][136][137] However, recent Omicron variants might exhibit reduced sensitivity to tixagevimab/cilgavimab. [138][139][140]…”

“…Tixagevimab/cilgavimab was recommended for pre‐exposure prophylaxis during the COVID‐19 pandemic, particularly for patients within 1 year of CAR‐T therapy 131,132 . As demonstrated, it may reduce the risk of severe infection and death in patients with breakthrough infections 131,133–137 . However, recent Omicron variants might exhibit reduced sensitivity to tixagevimab/cilgavimab 138–140 …”