In a single-institution prospective cohort study (CANVAX Cohort Study) reported in the Journal of Clinical Oncology, Naranbhai and colleagues assessed the immunogenicity of SARS–CoV-2 vaccines in patients with cancer. They found that immunogenicity varied among vaccines and that both antibody concentrations and neutralization titers were lower than those in healthy controls.
Study Details
The study included 762 eligible patients with solid organ or hematologic cancers enrolled at Massachusetts General Hospital Cancer Center between April 29 and July 20, 2021, who had received two doses of mRNA-1273 (Moderna; 37.8%) or BNT162b2 (BioNTech/Pfizer; 50.3%) or one dose of Ad26.COV2.S (Johnson & Johnson; 11.9%) vaccines. Anti–SARS–CoV-2 immunoglobulin A/M/G spike antibodies, neutralization, and reactogenicity were assessed at least 7 days following completed vaccination.
Neutralization data were available for 655 patients. Findings were compared with those in 1,638 healthy controls. Overall, 9% of the cohort was non-White, 71.5% had solid organ malignancies, and 27% were not receiving cancer-directed systemic therapy.
Key Findings
Among patients with cancer, mRNA-1273 was the most immunogenic (log10 geometric mean concentration [GMC] = 2.9, log10 geometric mean neutralization titer [GMT] = 2.3), followed by BNT162b2 (GMC = 2.4; GMT = 1.9) and Ad26.COV2.S (GMC = 1.5; GMT 1.4); on multivariate analysis, both GMC and GMT were significantly lower with BNT162b2 and Ad26.COV2.S (P < .001 for all). The proportion of low neutralization (< 20% of convalescent titers) among Ad26.COV2.S recipients was 69.9%.
In an analysis adjusting for age, time of sampling, and vaccine, antibody titers (–0.6 log10 U/mL, 95% confidence interval [CI] = –0.80 to –0.41, P < .001) and neutralization titers (–0.35 log10 U/mL, 95% CI = –0.06 to –0.03, P < .0001) were significantly lower in patients with cancer than in comparable healthy controls.
Among patients with cancer, receipt of chemotherapy in the preceding 12 months was associated with lower antibody concentrations (–0.29 log10 U/mL, 95% CI = –0.44 to –0.14, P < .001) and neutralization titers (–0.21, 95% CI = –0.32 to –0.09, P < .001). Current receipt of corticosteroids was associated with lower antibody concentrations (–0.37; 95% CI, –0.61 to –0.12, P = .003) and a trend toward lower neutralization titers (–0.15, 95% CI = –0.33 to 0.03, P = .09). Receipt of immune checkpoint blockade in the preceding 12 months was associated with a trend toward higher neutralization titers (0.13, 95% CI = –0.01 to 0.27, P = .063).
Prior COVID-19 infection (7.1% of the cohort) was associated with higher antibody responses (P < .001). In 32 patients who received an additional vaccine dose, 30 exhibited increased antibody titers after the dose (GMC = 1.05 before and 3.17 after).
The incidence of local or systemic reactogenicity symptoms was highest in mRNA-1273 recipients (81%), followed by BNT162b2 recipients (72%) and Ad26.COV2.S recipients (42%; overall P < .001). Systemic reactogenicity was positively correlated with both antibody concentration (P = .002) and neutralization titers (P = .016).
The investigators concluded: “Immune responses to SARS–CoV-2 vaccines are modestly impaired in patients with cancer. These data suggest utility of antibody testing to identify patients for whom additional vaccine doses may be effective and appropriate, although larger prospective studies are needed.”
Justin F. Gainor, MD, of Massachusetts General Hospital Cancer Center, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Lambertus Family Foundation; Donald Glazer Fund, and others. For full disclosures of the study authors, visit http://ascopubs.org.
