In a large population of patients with solid tumours undergoing active anticancer treatment, the researchers confirmed a favourable safety profile of mRNA-BNT162b2 vaccine, which may reassure on maintaining active anticancer treatment throughout the whole vaccination schedule. Humoral response to first vaccine dose was inadequate, but the second, booster dose resulted in an exponential increase in IgG titre and high rate of seroconversion, arguing against delays in dosing schedule. Although some clinical features predict reduced immunogenicity, further investigation is required to confirm their significance. The findings from the Vax-On study are published online on 19 September 2021 in the Annals of Oncology by Dr. Fabrizio Nelli of the Department of Oncology and Haematology, Medical Oncology Unit, Central Hospital of Belcolle in Viterbo, Italy and colleagues.
In the Vax-On observational study, the study team assessed the effects of active anticancer treatment on safety and immunogenicity of mRNA-BNT162b2 vaccine in patients with solid tumours. They prospectively enrolled patients who started the 3-week apart mRNA-BNT162b2 vaccine schedule from 9 March to 12 April 2021 (timepoint 1). Those on active anticancer treatment within the previous 28 days accounted for the exposed cohort. Patients who had discontinued anticancer treatment by at least 28 days represented the control cohort. Safety analysis and quantification of anti-SARS-CoV-2 Spike IgG were performed before the second dose (timepoint 2) and 8 weeks thereafter (timepoint 3).
The titration was performed using the Abbott SARS-CoV-2 chemiluminescent microparticle immunoassay and seroconversion was defined at ≥50 AU/mL IgG titre. No SARS-CoV-2 rRT-PCR swab test or serologic titre was required at baseline. The study was approved by referring ethics committee and formally registered (EudraCT N.2021-002611-54).
The study team enrolled 366 patients of whom 285 in exposed cohort and 81 in the control cohort. The cohorts were mostly homogeneous. The adjuvant chemotherapy setting, prevalent in control cohort, accounts for the difference. Severe adverse events were rare, observed in just 1%. The most common adverse reactions were mild injection site reactions. Systemic adverse events did not exceed 17% of cases and were significantly associated with female sex, ECOG performance status 2 or G-CSF use.
At timepoint 2, the median IgG titre of 131 AU/ml (95% confidence interval [CI] 77-173) versus 62 AU/ml (95% CI 42-82) with p value of 0.029, median log IgG titre with p value of 0.033, and seroconversion rate of 65% versus 52% with p value of 0.048 were significantly higher in control cohort.
The median IgG titre, median log IgG titre, and percentage of seroconverted patients in control and exposed cohorts did not differ at timepoint 3. A significant 15-fold or greater increase in median IgG titres and seroconversion rates up to 91% were observed from timepoint 2 to 3 within the same cohorts (p < 0.001).
Multivariate analysis did not confirm a negative interaction between cytotoxic chemotherapy and antibody response, but ECOG performance status 2 and G-CSF use were significantly associated with lower IgG titre and lack of seroconversion after either dose of vaccine.
The authors concluded about a favourable safety profile of mRNA-BNT162b2 vaccine in patients with solid tumours during active anticancer treatment. They commented that patients with specific conditions, such as female sex and use of G-CSF, should be cautioned about increased risk of side effects. Although some clinical features predict reduced immunogenicity, further research is needed to confirm their significance.
Nelli F, Fabbri A, Onorato A, et al. Effects of active cancer treatment on safety and immunogenicity of COVID-19 mRNA-BNT162b2 vaccine: Preliminary results from the prospective observational Vax-On study. Annals of Oncology; Published online 19 September 2021. DOI: https://doi.org/10.1016/j.annonc.2021.09.009