To the Editor:

As a new wave of coronavirus disease 2019 (COVID-19) is spreading across Europe, and Omicron variant emerging as a new threat, important data regarding the six-month efficacy and toxicity profile of the BNT162b2 mRNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with solid tumors have recently been provided.1 Vaccine protection was shown to significantly decrease at six months post vaccine among adults with cancer, suggesting that this population requires subsequent measures of COVID-19 risk reduction, such as vaccine booster. Intriguingly, they report that age was not associated with vaccine response.

Adolescents and young adults (AYAs) with cancer are at high risk of severe forms of COVID-19 compared with the general population of AYAs.2 Our group published the first data on BNT162b2 vaccine short-term efficacy in a cohort of AYAs with various types of solid tumors that showed a high rate of seroconversion.3 Furthermore, in the general population, the BNT162b2 vaccine produced a greater long-term immune response in young adults than in older people.4 The conclusions drawn from the study of Waldhorn et al. may thus not be extrapolated to AYAs with cancer for whom data regarding the mid- and long-term vaccine efficacy are still lacking.

To study the six-month BNT162b2 vaccine efficacy profile in AYAs, we reviewed the six-month follow-up data from our cohort of patients aged 16–21 years. Among the 13 patients included in the first report, three patients had no follow-up data at six months (disease progression in two patients and loss of follow-up in one patient). A new patient who was previously treated in another cancer center was included at six months post vaccine. Overall, out of the 32 patients under surveillance for BNT162b2 vaccine efficacy and safety in our center (APHM PADS21-136), 11 patients reached six-month follow-up.

Among these 11 patients, two patients did not show seroconversion despite a complete two-dose vaccine schedule. The reasons for the absence of immunization in this subset of patients remain unclear. The intensity and/or duration of anticancer treatment may cause this poor response. Both patients were heavily treated with intensive chemotherapy and radiotherapy for high-risk diseases.

After six months post vaccine, the other nine out of 11 patients showed persistent anti-S1 IgG antibodies (median 446 BAU/ml (binding antibody units/ml), range 208–3219 BAU/ml), as shown in the Figure 1. In these patients, the antibody levels decreased over time, but remained above or close to the level previously reported to be associated with an 80% postadenoviral vaccine protection against SARS-CoV-2 (264 BAU/ml).5 Neutralizing antibodies were detected in all of these patients (data not shown). Waldhorn et al. reported that the patients’ serology titers dramatically decreased at six months post vaccine but did not provide the antibody levels data, hampering direct comparison.

Evolution of anti-S1 IgG antibody levels. Anti-S1 antibodies were quantified using the ELISA kit anti-SARS-CoV-2 QuantiVac (IgG) - Euroimmun, Lübeck, Germany (binding antibody units [BAU] per milliliter). The red zone indicates negative serology (25.6 BAU/ml) inferior or superior to the antibody level associated with protection against SARS-CoV-2 (264 BAU/ml), respectively5

Our observations suggest that AYAs with cancer may show a more durable protection from COVID-19 six months after BNT162b2 vaccination, as compared with older adults. However, the overall decrease in titers over time, the dispersion of residual titers at six months, and the existence of residual titers close to the cutoff value of 264 BAU/ml suggest that a quantitative serological follow-up is required. More data are needed regarding the impact of age and anticancer treatment intensity and duration on vaccine immunogenicity. Conducting anti-SARS-CoV-2 vaccine efficacy studies for each age group in oncology is of utmost importance to determine the necessity and optimal timing of a third vaccine administration.

ACKNOWLEDGMENTS

The authors thank Paola Saba Villarroel, PhD, Abdennour Amroun, PhD, Elif Nurtop, PhD, and Toscane Fourié, PhD for assistance with the experiments and the patients and their family for participation in the study.

CONFLICT OF INTEREST

Caroline Donze, Laetitia Ninove, and Xavier de Lamballerie have no conflict of interest to disclose. Paul Saultier reports receiving support for attending scientific meetings and educational events from Baxalta-Shire, Novo Nordisk, Pfizer, Octapharma, Roche, Servier, and Sobi and has received honoraria (consultant on advisory boards) from Octapharma outside the area of the submitted work. Nicolas Andre reports receiving grants and/or drugs for trials from Bristol Myers Squibb and Pierre Fabre, outside the area of submitted work; receiving travel support from Bristol Myers Squibb; and participating as a scientific advisory board member (without receiving personal fees) for Bayer and Bristol Myers Squibb, and Partners Therapeutics, outside the area of the submitted work.

AUTHOR CONTRIBUTIONS

Caroline Donze and Paul Saultier wrote the paper. Laetitia Ninove and Xavier de Lamballerie supervised and interpreted the biological analyses. Caroline Donze, Paul Saultier, and Nicolas Andre collected clinical data. Xavier de Lamballerie, Paul Saultier, and Nicolas Andre coordinated the study. All authors edited and approved the final manuscript as submitted and agree to be accountable for all aspects of the work.