Single-dose BNT162b2 COVID-19 vaccine inadequate in cancer patients

One dose of the BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine yields poor efficacy in patients with solid or haematological cancer, but immunogenicity increases significantly in those with solid cancer following a second dose given on day 21 after the first dose, a prospective observational study has shown.

These interim findings, from the first report of safety and immunogenicity of any COVID-19 vaccine in immunocompromised patient populations, support prioritization of cancer patients for early administration of a second dose of BNT162b2 on day 21 after the first dose. [Lancet Oncol 2021;doi:10.1016/S1470-2045(21)00213-8]

The study included 151 patients with solid (n=95) or haematological (n=56) cancer and 54 healthy controls (mostly healthcare workers) recruited from three hospitals in London, UK, between 8 December 2020 and 18 February 2021.

Following vaccination with the first 30 μg dose of BNT162b2 in all cancer patients on day 1, 25 patients with solid tumours and six patients with haematological malignancies received a second dose on day 21, while a delayed boost at around 12 weeks was scheduled for 69 and 49 patients, respectively.

Among healthy controls, 16 received two doses of the vaccine over a 21-day interval, while a 12-week boost was planned for the remaining 38.

The current interim analysis included samples and data obtained up to 19 March 2021, with 17 participants excluded from the immunogenicity analysis due to evidence of previous exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

“A single dose of 30 μg BNT162b2 failed to induce seroconversion in most patients with cancer,” the investigators reported.

At approximately 21 days following vaccination with the first dose, positive anti–SARS-CoV-2 spike protein immunoglobulin G antibody (anti-S IgG) titres were detected in only 21 of 56 patients (38 percent) with solid cancer and eight of 44 patients (18 percent) with haematological cancer, compared with 32 of 34 healthy controls (94 percent).

“Maximum anti-S IgG titres were approximately 100 times higher than minimum responses, but median titres were largely similar in each cohort. Thus, the main difference between healthy controls and cancer patients was failure to produce a response, rather than the magnitude of response,” the investigators explained. “Failure to produce a response to first-dose vaccination was not obviously attributable to age.”

Within 2 weeks of a vaccine boost given on day 21 after the first dose, immunogenicity was found to have significantly increased in patients with solid cancer.

Among those with available blood samples 2 weeks after a 21-day vaccine boost, seropositivity was found in 18 of 19 patients (95 percent) with solid cancer, three of five patients (60 percent) with haematological cancer, and 12 of 12 healthy controls (100 percent).

Among those who did not receive a second dose of BNT162b2, 10 of 33 patients (30 percent) with solid cancer, four of 36 patients (11 percent) with haematological cancer, and 18 of 21 healthy controls (86 percent) were seropositive 5 weeks after the first dose.

The BNT162b2 vaccine was well tolerated, with no toxicities reported in 75 of 140 cancer patients (54 percent) after the first dose and 22 of 31 cancer patients (71 percent) after the second dose. Injection-site pain within 7 days after the first dose was the most common local reaction, reported in 23 of 65 cancer patients (35 percent).

“Our data support prioritization of patients with cancer for an early day-21 second dose of the BNT162b2 vaccine,” the investigators suggested. “Given the globally poor responses to vaccination in patients with haematological cancer, post-vaccination serological testing and careful follow-up should be prioritized for these patients together with vaccination of those in close contact with them, in order to promote herd immunity.”

“The impact of boosting in patients with haematological cancer will be determined through ongoing follow-up,” they added.