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Humoral Response to the Third Dose of the mRNA-based COVID-19 Vaccine in a Large Cohort of Patients with Cancer

Most patients were on active anticancer treatment during the 28 days before the administration of third dose
04 Mar 2022
Cancer in Special Situations / Population

In a letter to editor published on 21 February 2022 in the Annals of Oncology, Dr. Vincenzo Di Noia of the Medical Oncology, Regina Elena National Cancer Institute in Rome, Italy and colleagues described the serological response to the third dose of the BNT162b2 mRNA COVID-19 vaccine in a large cohort of patients with cancer. Most patients were on active anticancer treatment during the 28 days before the administration. The results show overall positive response to the additional dose of COVID-19 vaccine. The present study is still ongoing to evaluate the durability of immune response to the additional dose in a long-term period. Although a very high seroconversion rate followed the additional dose, there was also a very small subgroup of patients with no detectable humoral response even after the third vaccine dose.

The study team previously showed the rapid decline of humoral response over time until 6 months of follow-up in their cohort of patients with cancer after the first and the second BNT162b2 mRNA COVID-19 vaccine doses. Now they report in the Annals of Oncology that from September to November 2021, in their cohort 407 patients received the additional third dose at 4-6 months after the completion of the primary vaccine series.

The median age of patients was 67 years (range 24-89). Most common tumour subtypes were breast cancer (28.5% patients) and lung cancer (19.9% patients). Majority of patients, 366 of 407 (89.9%) were on active anticancer treatment during the 28 days before the vaccine administration. Chemotherapy alone or in combination with monoclonal antibodies was the most used treatment (32.2%), followed by targeted therapy (22,8%) and immune checkpoint inhibitors (15.7%). Chronic steroid use with daily assumption started at least 30 days before the vaccination was reported in 48 patients (11.8%).

Vast majority of patients had a positive serological status after the third vaccine dose, in particular 402 of 407 patients (98.8%). All 5 non-responding patients had a negative serological status also at pre-dose assessment, although one patient was seropositive after the second dose. Among 5 patients who remained sero-negative after the additional dose, 4 patients (80%) were on active treatment, 1 with chemotherapy, 2 with targeted therapy, and 1 with immunotherapy.

The geometric mean concentration (GMC) of anti-S IgG reached after the booster was 1054.5 AU/ml. Analysis of post-dose IgG titre according to clinical characteristics showed that only chronic use of steroids was significantly associated with lower antibodies level (p = 0.035). The type of anticancer treatment did not significantly affect the IgG titre (p > 0.05). Only 193 patients were evaluated for IgG titre just before and at 4-weeks after the third dose. The GMC increased from 61.3 to 1280.4 AU/ml with statistically significant increase of 20.9-fold (p < 0.001). Considering the 258 patients who were evaluated for IgG titre at 4-weeks after the second and third doses, the GMC significantly increased 5.77-fold, from 215.2 AU/ml post-second dose to 1240.6 AU/ml after the booster (p < 0.001).

No severe adverse events after the third dose were observed.

The authors commented that for patients with no detectable humoral response even after the third dose, further studies are warranted to assess the existence of other types of immunity (e.g. T-cell immunity) and to explore its correlation with protection from infection.

The authors also commented that the active anticancer treatment did not affect the serological immune response to the third COVID-19 vaccine dose and patients receiving chemotherapy seems not have weaker humoral response compared with patients undergoing other types of anticancer treatment. The chronic use of steroids was associated with a weaker humoral response also for the third vaccine dose.

The authors thanked the staff of IRCCS Regina Elena National Cancer Institute in Rome, Italy for their commitment to the COVID-19 vaccination campaign for patients with cancer. 


Di Noia V, Pimpinelli F, Renna D, et al. Potentiation of humoral response to BNT162b2 vaccine after the third dose in patients with solid cancer. Annals of Oncology; Published online 21 February 2022. doi: https://doi.org/10.1016/j.annonc.2022.02.006

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