Efficacy of the mRNA-Based BNT162b2 COVID-19 Vaccine in Patients with Solid Malignancies Treated with Anti-Neoplastic Drugs

Abstract

The BNT162b2 vaccine was shown to be highly effective in reducing the risk of COVID-19 infection in healthy individuals and patients with chronic disease. However, there are little data regarding its efficacy in patients treated for cancer. We analyzed the humoral response following vaccination with the second dose of BNT162b2 in 140 patients with solid malignancies who were receiving anti-cancer therapy at the time of vaccination and 215 participants who had not been diagnosed with cancer. Multivariate analysis was performed, followed by matching the two groups by age, gender and days from vaccination. The humoral response in the cancer patient group was significantly lower than in the non-cancer group: 20/140 seronegative (14.3%) vs. 3/215 (1.4%), p < 0.001; median IgG levels 2231 AU/mL (IQR 445-8023) vs. 4100 (IQR 2231-6774) p = 0.001 respectively. The odds ratio for negative serology results in cancer patients adjusted by age and gender was 7.35 compared to participants without cancer. This effect was observed only in chemotherapy treated patients: 17/73 seronegative (23.3%) vs. 3/215 (1.4%), p < 0.001; median IgG 1361 AU/mL vs. 4100, p < 0.001 but not in patients treated with non-chemotherapeutic drugs. Reduced immunogenicity to COVID-19 vaccine among chemotherapy-treated cancer patients, raises the need to continue exercising protective measures after vaccination in these patients.

Keywords: COVID-19 vaccine; SARS-CoV-2; antibody response; cancer; chemotherapy; immunotherapy.

Figure 1

Vaccine response: (A) percent of seronegative patients with cancer (blue bars) and non-cancer participants (maroon bars) in unmatched analysis (cancer patients, n = 140; controls, n = 215, p < 0.001) and matched analyses (±14 days following second vaccine dose, n = 99 pairs, p = 0.004; and ±7 days following second vaccine dose, n = 82 pairs, p = 0.057); (B) percent of seronegative cancer patients undergoing chemotherapy at the time of vaccination (green bars) compared to non-cancer participants (maroon bars) in unmatched analysis (cancer patients, n = 73; controls, n = 215, p < 0.001) and matched analyses (±14 days, n = 57 pairs, p = 0.007; and ±7 days, n = 45 pairs, p = 0.039); (C) percent of seronegative cancer patients undergoing non-chemotherapy treatment at the time of vaccination (blue bars) compared to controls (maroon bars) in unmatched analysis (cancer patients, n = 67; controls, n = 215) and matched analyses (±14 days, n = 42 pairs; and ±7 days, n = 37 pairs). In all analyses, the differences were not significant (NS); (D) in the unmatched analysis, percent of seronegative participants in the subgroups of patients undergoing chemotherapy treatment (Tx) (n = 73), non-chemotherapy treatment (n = 67), and comparison group (n = 215).

Figure 2

SARS-CoV-2 IgG antibodies titer. Violin graphs and box plots of the distribution of anti-SARS-CoV-2 antibody levels (AU/mL). The median and quartiles are presented as horizontal lines within the box plot. (A) Cancer and comparison non-cancer groups (unmatched). The median SARS-CoV-2 IgG levels, (2231 AU/mL) were significantly lower in the cancer group than in the comparison group, median 4100 AU/mL, (p = 0.001). The lower IgG values are more frequent in the cancer group; (B) chemotherapy-treated, non-chemotherapy-treated and comparison groups (unmatched). The lower IgG values, as apparent from the wider bottom distribution, are more frequent in the chemotherapy treated group. The antibody levels in the chemotherapy group, median 1361 AU/mL, but not in the non-chemotherapy group, median 5088 AU/mL, are significantly lower than the comparison group, median 4100 AU/mL, p < 0.001 and p = 0.627 respectively. Median immunoglobulin levels, represented by the middle horizontal lines, were significantly lower in the chemotherapy-treated patients: 1361 AU/mL versus 5088 AU/mL in non-chemotherapy treated patients (p < 0.001).