Tixagevimab-cilgavimab (Evusheld) appears less effective against the omicron variant of SARS-CoV-2 in patients with hematologic cancer, according to research published in Cancer Cell.
Researchers found that a single 150 mg dose of tixagevimab-cilgavimab demonstrated neutralizing activity against wild-type SARS-CoV-2 but not the omicron variant.
The current recommended dose, 300 mg, seemed to be more effective against omicron than the 150 mg dose, but results varied.
Tixagevimab-cilgavimab is a combined monoclonal product intended to prevent COVID-19. It was authorized by the US Food and Drug Administration for emergency use in individuals age 12 years or older who are severely immunocompromised. However, the product was authorized before the evolution of the omicron variant.
Researchers conducted a prospective study to evaluate the efficacy of tixagevimab-cilgavimab against the omicron variant in patients with hematologic cancers.
The study included 52 patients. The most common diagnoses were chronic lymphocytic leukemia (n=15), other non-Hodgkin lymphomas (n=20), multiple myeloma (n=8), acute myeloid leukemia (n=6), and acute lymphoblastic leukemia (n=2).
Most patients (n=42) received a single dose of tixagevimab-cilgavimab at 150 mg, 5 patients received 2 doses at 150 mg, and 5 received a single dose at 300 mg.
The median time between the first 150 mg dose and sample collection was 33 days. After the first dose, all patients had high anti-spike immunoglobulin G (anti-S IgG) antibody titers — a median of 16,099.3 AU/mL.
However, the anti-S IgG titers were only consistent with activity against wild-type SARS-CoV-2, not the omicron variant, the researchers noted. Patients treated with a single 150 mg dose of tixagevimab-cilgavimab had “uniform and complete neutralization” of wild-type receptor binding domain (RBD), but the median neutralizing activity against omicron-RBD did not reach the positive cutoff value of 30%.
Patients treated with a second 150 mg dose and those treated with a single 300 mg dose had higher neutralization of omicron-RBD, when compared with the single 150 mg dose group (P =.003). Nine of the 10 patients had neutralizing activity above the positive cutoff value.
At a median follow-up of 79 days, there were 2 cases of SARS-CoV-2 infection reported. Both patients had received a single dose of tixagevimab-cilgavimab at 150 mg. Both patients were treated with sotrovimab and recovered without the need for hospitalization.
“[Tixagevimab-cilgavimab] failed to achieve meaningful neutralization of omicron-RBD in patients with hematologic malignancies treated with a single 150 mg dose,” the researchers wrote. “Neutralization significantly increased above the positive cutoff after a single 300 mg dose but remained heterogeneous.”
“Despite dampened activity against the omicron variant, [tixagevimab-cilgavimab] remains the only available preexposure prophylaxis agent,” the researchers added. “Vigilant behavior and vaccination when physiologically appropriate therefore remain the backbone of protection against SARS-CoV-2 in patients with hematologic malignancies. Identification and development of broadly neutralizing antibody therapies targeting highly conserved regions of the SARS-CoV-2 spike protein are needed in the face of a readily mutable pathogen.”
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Stuver R, Shah GL, Korde NS, et al. Activity of AZD7442 (tixagevimab-cilgavimab) against omicron SARS-CoV-2 in patients with hematologic malignancies. Cancer Cell. Published online May 16, 2022. doi:10.1016/j.ccell.2022.05.007