Reduced humoral immune response after BNT162b2 coronavirus disease 2019 messenger RNA vaccination in cancer patients under antineoplastic treatment

Abstract

Background: Cancer patients are at a higher risk of developing severe coronavirus disease 2019 (COVID-19). However, the safety and efficacy of COVID-19 vaccination in cancer patients undergoing treatment remain unclear.

Patients and methods: In this interventional prospective multicohort study, priming and booster doses of the BNT162b2 COVID-19 vaccine were administered 21 days apart to solid tumor patients receiving chemotherapy, immunotherapy, targeted or hormonal therapy, and patients with a hematologic malignancy receiving rituximab or after allogeneic hematopoietic stem cell transplantation. Vaccine safety and efficacy (until 3 months post-booster) were assessed. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD) antibody levels were followed over time (until 28 days after the booster) and in vitro SARS-CoV-2 50% neutralization titers (NT50) toward the wild-type Wuhan strain were analyzed 28 days after the booster.

Results: Local and systemic adverse events (AEs) were mostly mild to moderate (only 1%-3% of patients experienced severe AEs). Local, but not systemic, AEs occurred more frequently after the booster dose. Twenty-eight days after the booster vaccination of 197 cancer patients, RBD-binding antibody titers and NT50 were lower in the chemotherapy group {234.05 IU/ml [95% confidence interval (CI) 122.10-448.66] and 24.54 (95% CI 14.50-41.52), respectively} compared with healthy individuals [1844.93 IU/ml (95% CI 1383.57-2460.14) and 122.63 (95% CI 76.85-195.67), respectively], irrespective of timing of vaccination during chemotherapy cycles. Extremely low antibody responses were seen in hematology patients receiving rituximab; only two patients had RBD-binding antibody titers necessary for 50% protection against symptomatic SARS-CoV-2 infection (<200 IU/ml) and only one had NT50 above the limit of detection. During the study period, five cancer patients tested positive for SARS-CoV-2 infection, including a case of severe COVID-19 in a patient receiving rituximab, resulting in a 2-week hospital admission.

Conclusion: The BNT162b2 vaccine is well-tolerated in cancer patients under active treatment. However, the antibody response of immunized cancer patients was delayed and diminished, mainly in patients receiving chemotherapy or rituximab, resulting in breakthrough infections.

Keywords: BNT162b2 COVID-19 vaccination; anti-RBD IgG antibody response; antineoplastic treatment; cancer; safety.

Figure 1

Trial profile.

Figure 2

Local and systemic adverse events (AEs) reported within 7 days after priming and booster BNT162b2 vaccination. (A) Local and (C) systemic AEs have been pooled from all study cohorts and are represented as a percentage of the total study population (n = 200 for priming vaccination, n = 197 for booster vaccination). To show differences in the occurrence of AEs between study cohorts, the proportion of patients reporting AEs are represented as a percentage of the number of patients in that cohort (first vaccine dose: hematology cohort, n = 41; targeted/hormonal therapy cohort, n = 80; chemotherapy cohort, n = 63; immunotherapy cohort, n = 16; second vaccine dose: hematology cohort, n = 41; targeted/hormonal therapy cohort, n = 80; chemotherapy cohort, n = 60; immunotherapy cohort, n = 16) (B and D). Open bars represent the AEs reported after the first vaccine dose while the dashed bars represent the ones reported after the second vaccine dose. Comparisons between both vaccine administrations were performed using a McNemar test with Bonferroni-Holm correction for the number of cohorts (n = 4) and the number of different local AEs (n = 3) and systemic AEs (n = 7) are reported: ∗P < 0.05.

Figure 3

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-RBD antibody response generated after BNT162b2 vaccine administration. (A) SARS-CoV-2 anti-RBD immunoglobulin G (IgG) levels before the priming dose on day 0, 21 days after the priming dose, 7 and 28 days after the booster dose in the different study cohorts. (B and C) Differences between the subcohorts of the hematology and chemotherapy cohorts, respectively. All samples were analyzed using an ELISA for the quantitative detection of IgG class antibodies to RBD. Geometric mean titers (GMTs) of the anti-RBD antibody titers are presented with the dotted line indicating lower limit of quantification (LLQ). Values below the LLQ are imputed to half the LLQ. I bars indicate standard errors. RBD, receptor-binding domain.

Figure 4

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody response generated after BNT162b2 vaccine administration. Virus neutralizing test with neutralizing titer 50% neutralization titers (NT50) defined as the sample dilution (reciprocal titer) conveying 50% neutralization in SARS-CoV-2 (strain 2019-nCoV-Italy-INMI1, reference 008V-03893, passage 5) infected wells. (A) In vitro SARS-CoV-2 NT50 toward the wild-type Wuhan strain 28 days after the booster dose in the different study groups. (B) Correlation between SARS-CoV-2 anti-RBD immunoglobulin G (IgG) and NT50 with regression line for all values above the lower limit of quantification (LLQ). Geometric mean titers (GMTs) of the NT50 are presented, with the dotted line indicating LLQ. Values below the LLQ are imputed to 1/10 LLQ for NT50. I bars indicate standard errors.