Safety and immunogenicity of one versus two doses of the COVID-19 vaccine BNT162b2 for patients with cancer: interim analysis of a prospective observational study

Abstract

Background The efficacy and safety profiles of vaccines against SARS-CoV-2 in patients with cancer is unknown. We aimed to assess the safety and immunogenicity of the BNT162b2 (Pfizer–BioNTech) vaccine in patients with cancer. Methods For this prospective observational study, we recruited patients with cancer and healthy controls (mostly health-care workers) from three London hospitals between Dec 8, 2020, and Feb 18, 2021. Participants who were vaccinated between Dec 8 and Dec 29, 2020, received two 30 μg doses of BNT162b2 administered intramuscularly 21 days apart; patients vaccinated after this date received only one 30 μg dose with a planned follow-up boost at 12 weeks. Blood samples were taken before vaccination and at 3 weeks and 5 weeks after the first vaccination. Where possible, serial nasopharyngeal real-time RT-PCR (rRT-PCR) swab tests were done every 10 days or in cases of symptomatic COVID-19. The coprimary endpoints were seroconversion to SARS-CoV-2 spike (S) protein in patients with cancer following the first vaccination with the BNT162b2 vaccine and the effect of vaccine boosting after 21 days on seroconversion. All participants with available data were included in the safety and immunogenicity analyses. Ongoing follow-up is underway for further blood sampling after the delayed (12-week) vaccine boost. This study is registered with the NHS Health Research Authority and Health and Care Research Wales (REC ID 20/HRA/2031). Findings 151 patients with cancer (95 patients with solid cancer and 56 patients with haematological cancer) and 54 healthy controls were enrolled. For this interim data analysis of the safety and immunogenicity of vaccinated patients with cancer, samples and data obtained up to March 19, 2021, were analysed. After exclusion of 17 patients who had been exposed to SARS-CoV-2 (detected by either antibody seroconversion or a positive rRT-PCR COVID-19 swab test) from the immunogenicity analysis, the proportion of positive anti-S IgG titres at approximately 21 days following a single vaccine inoculum across the three cohorts were 32 (94%; 95% CI 81–98) of 34 healthy controls; 21 (38%; 26–51) of 56 patients with solid cancer, and eight (18%; 10–32) of 44 patients with haematological cancer. 16 healthy controls, 25 patients with solid cancer, and six patients with haematological cancer received a second dose on day 21. Of the patients with available blood samples 2 weeks following a 21-day vaccine boost, and excluding 17 participants with evidence of previous natural SARS-CoV-2 exposure, 18 (95%; 95% CI 75–99) of 19 patients with solid cancer, 12 (100%; 76–100) of 12 healthy controls, and three (60%; 23–88) of five patients with haematological cancers were seropositive, compared with ten (30%; 17–47) of 33, 18 (86%; 65–95) of 21, and four (11%; 4–25) of 36, respectively, who did not receive a boost. The vaccine was well tolerated; no toxicities were reported in 75 (54%) of 140 patients with cancer following the ...

Immune Responses to COVID-19 mRNA Vaccines in Patients with Solid Tumors on Active, Immunosuppressive Cancer Therapy

“…Our results agree with certain aspects of these findings, but differ with and extend upon several key points. As with a recent study on immunocompromised cancer patients 22 , we observed lower overall antibody and T cell responses compared with control cohorts. Yet in contrast to these findings, we observed that the majority of patients seroconverted after the first immunization, as measured by live virus neutralization assays.…”

“…A recent study in JAMA looked at 658 organ transplant recipients and demonstrated a lower antibody response after both doses of the mRNA COVID-19 vaccines when compared to immunocompetent participants 21 . Similarly, early studies suggest that cancer patients do not mount the same antibody responses as healthy controls 22 .…”

“…As another example, organ transplant recipients mount very poor antibody responses to the first mRNA immunization relative to healthy individuals 20 , but improve somewhat after the second immunization 21 . Similarly, in cancer patients with solid or hematological malignancies, antibody responses are also markedly diminished after the first immunization but often improve after the second 22 . Yet because a relatively small group of these cancer patients was tested after the second immunization and because this group contained a mixture of those on cytotoxic chemotherapy and checkpoint blockade therapy, more data are required to instruct how best to protect this vulnerable population.…”

CD8+ T cells contribute to survival in patients with COVID-19 and hematologic cancer

“…Finally, our finding that CD8 T cell immunity is critical for survival in patients with hematologic malignancy and COVID-19 has implications for the vaccination of these patients. The current Food and Drug Administration-approved COVID-19 mRNA vaccines induce robust CD8 T cell responses in addition to humoral responses [60][61][62][63] . Our findings suggest that vaccination of patients with hematologic cancer might provide protection through T cell immunity, despite the likely absence of humoral responses.…”

Emerging issues related to COVID-19 vaccination in patients with cancer

“…In the UK SOAP-02 study, 95 patients with solid cancer, 56 patients with hematological cancer, and 54 healthy controls (HC) were enrolled [ 29 ]. Of these, 31 patients with cancer and 16 HCs were vaccinated with two doses of the BNT162b2 vaccine 21 days apart, while the others received only the prime dose of the vaccine at the time of reporting, and were scheduled to receive the boost dose 12 weeks later.…”