Efficacy of Severe Acute Respiratory Syndrome Coronavirus-2 Vaccine in Patients With Thoracic Cancer: A Prospective Study Supporting a Third Dose in Patients With Minimal Serologic Response After Two Vaccine Doses

Abstract

Introduction: Coronavirus disease 2019 resulted in a 30% mortality rate in patients with thoracic cancer. Given that patients with cancer were excluded from serum antisevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine registration trials, it is still unknown whether they would develop a protective antispike antibody response after vaccination. This prospective vaccine monitoring study primarily aimed to assess humoral responses to the SARS-CoV-2 vaccine in patients with thoracic cancer.

Methods: SARS-CoV-2-spike antibodies were measured using the Abbot Architect SARS-CoV-2 immunoglobulin G immunoassay before the first injection of BNT162b2 mRNA vaccine, at week 4, and 2 to 16 weeks after the second vaccine dose administration. The factors associated with antibody response were analyzed.

Results: Overall, 306 patients, with a median age of 67.0 years (interquartile range: 58-74), were vaccinated. Of these, 283 patients received two vaccine doses at 28-day intervals. After a 6.7-month median follow-up, eight patients (2.6%) contracted proven symptomatic SARS-CoV-2 infection, with rapid favorable evolution. Of the 269 serologic results available beyond day 14 after the second vaccine dose administration, 17 patients (6.3%) were still negative (<50 arbitrary units/mL, whereas 34 (11%) were less than 300 arbitrary units/mL (12.5th percentile). In multivariate analysis, only age (p < 0.01) and long-term corticosteroid treatment (p = 0.01) were significantly associated with a lack of immunization. A total of 30 patients received a third vaccine dose, with only three patients showing persistently negative serology thereafter, whereas the others exhibited clear seroconversion.

Conclusions: SARS-CoV2 vaccines were found to be efficient in patients with thoracic cancer, most of them being immunized after two doses. A third shot given to 1% of patients with persistent low antibody titers resulted in an 88% immunization rate.

Keywords: Antibody response; COVID-19; Lung cancer; SARS-CoV-2; mRNA vaccine.

Figure 1

Serologic response to COVID-19 vaccine BNT162b2 in COVID-19–free patients. (A) Anti-S IgG antibody titers at day 0 in 137 patients without previous history of COVID-19; at day 28 after one vaccine dose injection in 248 patients without previous history of COVID-19; beyond day 42 in 248 patients without previous history of COVID-19; beyond day 21 after third vaccine dose in 30 patients with available results. Large horizontal bars represent the median value, with short bars illustrating the values of the first (lower) and third (upper) quartiles. Mann-Whiney U test was applied for statistical comparison. (B) Anti-S IgG antibody titers at day 28 after the first vaccine dose, according to the systemic treatment received within the previous 3 months: chemotherapy, including chemoimmunotherapy (n = 62), immunotherapy alone (n = 41), oral TKI or bevacizumab single-agent therapy (n = 34), or without systemic treatment (n = 111). Anti-S IgG antibody titers at day 28 in 18 healthy controls are illustrated. Large horizontal bars represent the median value, with short bars illustrating the values of the first (lower) and third (upper) quartiles. Mann-Whiney U test was applied for statistical comparison. (C) Anti-S IgG antibody titers at day 42 or beyond after the first vaccine dose, according to the systemic treatment received within the previous 3 months: chemotherapy, including chemoimmunotherapy (n = 58), immunotherapy alone (n = 41), oral TKI or bevacizumab single-agent (n = 36), or without systemic treatment (n = 113). Anti-S IgG antibody titers at day 42 in 13 healthy controls were available. Large horizontal bars represent the median value, with short bars illustrating the values of the first (lower) and third (upper) quartiles. Mann-Whiney U test was applied for statistical comparison. Anti-S, anti-SARS-CoV-2 anti-spike antibody; AU, arbitrary unit; COVID-19, coronavirus disease 2019; IgG, immunoglobulin G; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TKI, tyrosine kinase inhibitor.

Figure 2

Anti-S IgG antibody titers at D 28 and D 42 according to the different systemic treatments received. The horizontal dashed lines along the x axis indicate the limit of detection (positivity cutoff) provided by the manufacturer (log₁₀ 50 AU/mL). A nonparametric two-tailed pairwise comparison was performed using the Wilcoxon matched-pairs signed-rank test. Anti-S, anti-SARS-CoV-2 anti-spike antibody; AU, arbitrary unit; D, day; IgG, immunoglobulin G; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SABR, stereoteactic ablative radiotherapy; TKI, tyrosine kinase inhibitor.

Figure 3

(A) Evolution from D 0 of anti-S IgG antibody titers after a third vaccine dose injection in 26 patients with titers below 300 AU/mL on sampling after the second dose. The lower dashed line along the x axis indicates the limit of detection (positivity cutoff) provided by the manufacturer (log₁₀ 50 AU/mL). The upper dashed line along the x axis indicates log₁₀ 300 AU/mL cutoff. Statistical comparison used Mann-Whiney U test. (B) Comparison of anti-S IgG antibody titers at D 42 with titers after the third vaccine dose in 26 patients and with D 42 titers of 222 patients who received two doses. Statistical comparison used Mann-Whiney U test. Anti-S, anti-SARS-CoV-2 anti-spike antibody; AU, arbitrary units; COVID-19, coronavirus disease 2019; D, day; IgG, immunoglobulin G; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.