The accelerated development of multiple SARS-CoV-2 vaccines during the COVID-19 pandemic is unprecedented, and worldwide vaccination is ongoing. Among the commonly used COVID-19 vaccines are mRNA vaccines from Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273), and the vector-based vaccine from AstraZeneca (AZD1222). These vaccines are two-dose regimens, with the authorized intervals for administering the second dose set at 21 days, 28 days, and 4–12 weeks after the initial dose, respectively. However, due to limited vaccine supply and the ongoing pandemic, many health authorities have proposed prioritizing the delivery of a first vaccine dose in order to immunize as many people as possible and delaying the second booster vaccine dose. While this approach may be justified for healthy people younger than 65 years – assuming that a single dose of vaccine provides meaningful protection against COVID-19 – this may not apply to immunocompromised patients, such as cancer patients. Moreover, since patients with cancer, who are more likely to experience severe outcomes from contracting COVID-19, were not included in clinical trials of the vaccines, efficacy and safety data are limited for this group.

In the recently published SOAP-02 vaccine study, the safety and immunogenicity of the mRNA-based Pfizer-BioNTech vaccine was evaluated in patients with cancer, including the effect on seroconversion of a booster dose on day 21 after the first vaccine dose. The study was a prospective, longitudinal observational study of 151 patients with cancer (95 patients with solid cancer and 56 with hematologic cancer) and 54 healthy control individuals. All cancer patients were vaccinated on day 1, and 31 patients (25 with solid cancer; 6 with hematologic cancer) received a second dose on day 21. The remaining 118 patients (69 with solid cancer and 49 with hematological cancer) received a delayed dose, scheduled at around 12 weeks; 2 patients died due to COVID-19. Among healthy individuals, 16 received two doses 21 days apart, and the remaining 38 patients received a booster dose at 12 weeks. Blood samples were taken and assessed for immunogenicity of vaccine, measured by seroconversion rates, viral neutralization, and T-cell responses, at 3 weeks and 5 weeks after the first dose and 2 weeks after the booster dose for those who received it. Testing for antibody seroconversion identified 15 participants who had possible previous SARS-CoV-2 exposure, and a swab test identified 2 participants with current infection; these 17 participants were excluded from the analysis.

Results showed that at 21 days after the first dose of vaccine, seroconversion was induced in only 38% of patients with solid cancers and 18% of patients with hematological cancers, compared with 94% of healthy individuals. Of note, while a single vaccine dose failed to induce seroconversion in most cancer patients, those who did develop antibodies had a similar magnitude of response to the healthy controls. Evaluation of the effect of the booster dose showed that among participants who received a second dose on day 21, and who were available for analysis, 95% of patients with solid cancer, 60% with hematological cancers, and 100% of healthy controls had a positive antibody response. In contrast, among those who had not received a second booster dose, 30% of patients with solid cancer, 11% with hematological cancers, and 86% of healthy controls had a positive antibody response. Notably, statistical analysis showed that the impact of boosting versus not boosting on the immune status of patients with solid cancers was significant (P<0.0001), while the number of patients with hematological cancers was insufficient to assess this effect. Available toxicity data indicated that the vaccine was generally well tolerated. Of interest, patients with cancer reported less adverse events after the first and second doses of vaccine compared with healthy controls. Factors such as administration of vaccine within 15 days of cancer treatment, including chemotherapy with immune checkpoint inhibitors, and the use of steroids may be associated with poor seroconversion.

The investigators conclude that in this study – the first study to investigate the safety and immunogenicity of a COVID-19 vaccine in immunocompromised cancer patients – a single dose of the Pfizer-BioNTech vaccine resulted in poor immune efficacy in cancer patients and that a booster dose on day 21 had a significant positive impact on immunogenicity. Thus, patients with cancer and other high-risk immunocompromised groups should be prioritized to receive the second dose of the vaccine on day 21.

References

Monin L et al. Lancet Oncol. 2021 April 27. [Online ahead of print].