A Subset of Patients with NSCLC Respond Poorly to the COVID-19 mRNA Vaccines

A study of the vaccine-induced reactogenicity to COVID-19 mRNA vaccination in patients with non-small cell lung cancer (NSCLC) with emphasis on the antibody response to SARS-CoV-2 variants of concern including the Omicron variant revealed that although most patients with NSCLC generated a vaccine-specific antibody response comparable with the healthy volunteers, a subset of patients responded poorly to vaccination. Antibody titers in patients with NSCLC correlated with age, as patients older than 70 years had lower vaccine-induced antibody titers compared with younger patients. The study team led by Prof. Rafi Ahmed of the Emory University School of Medicine in Atlanta, GA, US did not find a correlation with the type of cancer treatment and the magnitude of the antibody response. The findings are published on 27 June 2022 in the Journal of Clinical Oncology.  

The authors wrote in the study background that the median age at lung cancer diagnosis is 70 years and because of immune dysregulation related to malignant disease and immunomodulatory therapies seen during lung cancer, it is important to evaluate the immune response after SARS-CoV-2 vaccination in these patients. Recent studies in patients with thoracic cancer receiving the BNT162b2 vaccine (99.3%) have shown to be efficient in generating protective antibody responses against the SARS-CoV-2 wild-type strain. However, vaccine-induced immune response to emerging variant of concerns in patients with NSCLC has not been studied in detail.

The study team examined the binding and neutralising antibody responses to SARS-CoV-2 wild type strain and Omicron variant in patients with NSCLC after primary mRNA vaccination and after booster dose. A total, 82 patients with NSCLC and 53 healthy volunteers who received COVID-19 mRNA vaccines were included in the study. Blood was collected longitudinally, and SARS-CoV-2–specific binding and neutralising antibody responses were evaluated.

A majority of patients with NSCLC generated binding and neutralising antibody titers comparable with the healthy vaccinees after COVID-19 mRNA vaccination, but a subset of 25% of patients with NSCLC made poor responses, resulting in overall lower (6- to 7-fold) titers compared with the healthy cohort (p ≤ 0.0001).

Although patients age older than 70 years had lower immunoglobulin G titers (p ≤ 0.01), patients receiving anti-PD1 monotherapy, chemotherapy, or a combination of both did not have a significant impact on the antibody response. Further studies with larger cohorts may be required to address if cancer therapy influences antibody response to SARS-CoV-2 vaccination.

Neutralising antibody titers to the Delta, Beta, and in particular, Omicron variants were significantly lower (p ≤ 0.0001) compared with the wild type strain. Booster vaccination led to a significant increase (p = 0.0001) in the binding and neutralising antibody titers to the wild type and Omicron variant. However, 2-4 months after the booster, the study team observed a 5- to 7-fold decrease in neutralizing titers to wild type and Omicron. These data highlight the concern for patients with cancer given the rapid spread of Omicron variant.

The authors commented that it is important to perform additional studies to identify the underlying mechanisms for the poor antibody responses and these studies should also examine vaccine-induced T-cell responses to determine if both cellular and humoral immune responses are compromised. A better understanding of the critical issues will provide insight into optimising vaccination strategies for patients with lung cancer, not only for COVID-19 disease, but also more broadly for vaccines in general.

This work was supported in part by grants from the US National Institute of Allergy and Infectious Diseases and other non-profit funds.  


Valanparambil RM, Carlisle J, Linderman SL, et al. Antibody Response to COVID-19 mRNA Vaccine in Patients With Lung Cancer After Primary Immunization and Booster: Reactivity to the SARS-CoV-2 WT Virus and Omicron Variant. JCO; Published online 27 June 2022. DOI: 10.1200/JCO.21.02986