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Antibody Response to SARS–CoV-2 Wild-Type Virus and Variants After mRNA Vaccination in Patients With NSCLC


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In a single-institution study reported in the Journal of Clinical Oncology, Valanparambil et al found that one-quarter of patients with non–small cell lung cancer (NSCLC) had poor antibody responses to the SARS–CoV-2 wild-type (WT) strain after mRNA vaccination, and that neutralizing antibody responses to the delta, beta, and—particularly—omicron variants were significantly poorer vs response to the WT strain among all patients. Receipt of a booster dose induced a transient improvement in response to the omicron variant.

Study Details   

The study included 82 patients with NSCLC and 53 healthy volunteers at Emory University School of Medicine who received SARS–CoV-2 mRNA vaccines. Vaccine-induced binding and neutralizing antibody responses to the SARS–CoV-2 WT strain (614D) and delta (B.1.617.2), beta (B.1.351), and omicron (B.1.1.529) variants were assessed 1 month after the primary two-dose regimen, and to the WT strain and omicron variant 1 month after a booster dose.

Key Findings 

After two doses, the majority of patients developed binding and neutralizing antibody titers vs the WT strain comparable to those in healthy controls.  However, approximately 25% of patients had poor antibody responses, including approximately 18% of patients with no detectable neutralizing antibody titers. Overall, neutralizing antibody titers in patients were sevenfold lower vs those in healthy controls (P = .0001).

In analysis of potential factors associated with poor responses, significantly lower spike-specific IgG titers were observed in patients aged > 70 years vs < 60 years and in recipients of the BNT162b2 vs mRNA-1273 vaccine (potentially related to the mRNA dose of 30 µg in the former vs 100 µg in the latter). No effect on antibody response was observed according to whether patients were receiving PD-1 targeted therapy alone or with chemotherapy, chemotherapy alone, other targeted therapy, or no therapy.  

Patients exhibited 6.5-, 14-, and > 50-fold lower neutralizing antibody titers against the delta, beta, and omicron variants vs the WT strain. 

Analysis of 24 patients receiving a booster dose at 8 months after primary vaccination showed significant increases in binding and neutralizing antibody titers to the WT strain and omicron variant (all P ≤ .0001). However, five- to sevenfold decreases in neutralizing antibody titers to both were observed two to four months after the booster dose.       

The investigators concluded, “A subset of patients with NSCLC responded poorly to the SARS–CoV-2 mRNA vaccination and had low neutralizing antibodies to the B.1.1.529 omicron variant. Booster vaccination increased binding and neutralizing antibody titers to omicron, but antibody titers declined after 3 months. These data highlight the concern for patients with cancer given the rapid spread of [the] SARS–CoV-2 omicron variant.”

Rafi Ahmed, PhD, of the Emory Vaccine Center, Department of Microbiology and Immunology, Emory University School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the National Institute of Allergy and Infectious Diseases, National Cancer Institute, and others. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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