Ella Roelant (Clinical Trial Center (CTC), CRC Antwerp, Antwerp University Hospital, University of Antwerp; StatUa, Center for Statistics, University of Antwerp) for statistical support, and Lise Verbruggen, MSc (Multidisciplinary Oncological Centre Antwerp (MOCA), Antwerp University Hospital), Dr. days after third BNT162b2 dose in 141 oncohematological patients (Suppl. Table 1). From the 200 initial participants that were included in the B-VOICE study2, 141 were evaluable after third dose. Drop-out was due to demise (20 participants, 10.0%), postponed vaccination due to illness or disease progression (8 participants, 4.0%), vaccination outside study protocol (5 participants, 2.5%) and consent withdrawal (26 participants, 13.0%). All subjects were assigned to a cohort based on the treatment type receiving at time of the third dose administration. Subjects with a solid tumor were divided into four treatment cohorts: chemotherapy, immunotherapy, targeted/hormonal therapy and chemotherapy + immunotherapy. A differentiation for patients with hematological malignancies was made between patients receiving rituximab and patients who have had undergone hematopoietic stem cell transplantation (HSCT) more than one year ago. An additional cohort was created for 7 subjects with hematological malignancy and 13 subjects with solid tumors that were no longer receiving active therapy at the time of third dose. A third BNT162b2 vaccination dose was administered 183 10 days (6 months) for 97% and 169-200 days for 3% of the subjects, after administration of the second BNT162b2 dose. Log-transformed antibody titers were compared using a random intercept linear Aldosterone D8 mixed model including time, treatment at time of sampling and the interaction between time and treatment at time of sampling. Anti-RBD IgG titers had waned significantly at six months post-second dose (GMT 65.8BAU/mL [95% CI 48.0-90.2] versus GMT 386.2BAU/mL [95% CI 253.3-588.7], p 0.0001). Administration of a third dose of BNT162b2 induced significantly higher anti-RBD IgG titers 28 days post-third dose in comparison to 28 days post-second dose (GMT 936.5BAU/mL [95% CI 600.5-1460.4], versus GMT 386.2BAU/mL [95% CI 253.3-588.7], p 0.0001). In comparison to other treatment cohorts, significantly lower anti-RBD IgG titers 28 days after second dose and 28 days post third dose could be observed in the rituximab cohort, with only few additional seroconverted patients after third dose (Figure 1 ). Open in a separate window Figure 1 SARS-CoV-2 anti-RBD IgG antibody titers before and after a third dose BNT162b2 in cancer patients. SARS-CoV-2 anti-receptor-binding domain (RBD) IgG antibody titers 28 days and six months after second BNT162b2 dose and 28 days after third BNT162b2 mRNA COVID-19 vaccine in the different treatment cohorts. Subjects were assigned to treatment cohorts based on the therapy received at time of the third dose. The height of each bar represents the geometric mean titer (GMT). All samples were analyzed using an enzyme-linked immunosorbent assay (ELISA) for the quantitative detection of IgG-class antibodies to RBD (BAU/mL). The dotted line indicates the lower limit of quantification (LLQ) of 5.4 BAU/mL. Values below this detection limit were imputed to half the LLQ. bars indicate standard errors. A significant decrease in anti-RBD IgG titers at six months post-second BNT162b2 dose, was observed in all treatment cohorts. Although waning anti-RBD IgG levels after primo-vaccination are also observed in healthy controls8, the percentual decrease in anti-RBD IgG titers at six months after primo-vaccination is much lower than the decrease reported in cancer patients. Considering the investigation that cancer patients have reduced humoral immune responses after dual-dose BNT162b2 vaccination compared to healthy controls2, this observation highlights the importance of prioritizing the administration of a third vaccination dose in cancer patients. The significant increase in antibody response upon a third dose is an Aldosterone D8 important observation indicating the successful generation of memory B-cells after primo vaccination9. However, in patients receiving rituximab, a third dose hardly induced any humoral immune response as rituximab depletes B-cells10. Hence, the role of a third dose remains debatable in this population, although adaptive cellular immunity after vaccination might play a role in protecting these patients against SARS-CoV-210. In conclusion, most patients after hematopoietic stem cell transplantation (HSCT) or with solid tumors, including those under active anti-cancer treatment, will benefit from a third dose of BNT16b2 vaccine. However, as a true serological correlate Aldosterone D8 of protection is not yet established, future research on post-vaccine antibody durability should be coupled to measurement of Rabbit Polyclonal to PDCD4 (phospho-Ser67) B-cell and T-cell responses over time. Declaration of Competing Interests The authors declare the following financial interests/personal relationships which may be considered.