ABSTRACT
Background: Real world studies on the immunogenicity of BNT162b2 and mRNA-1273 in patients (pts) with cancer showed a reduced seroconversion. The aim of the study is to evaluate the immunogenicity and clinical efficacy of two doses of mRNA vaccines in cancer pts, during or after active treatment. Patients and Methods: This is a single institution, prospective, observational study, conducted at Luigi Sacco Hospital in Milan, IT. Seric antibody levels were measured in solid cancer pts and in healthy controls before the 1st dose (T0) and 30 days after the 2nd one (T1) by a fluorescence bead-based assay. Seroconversion (SR) was defined as anti-S and anti-RBD > 700 MFI (Median Fluorescence Intensity). Previous exposure was defined as anti-N >700 MFI (E-group: exposed;nonE-group: non exposed). Clinical efficacy was defined as the percentage of subjects who did not develop COVID-19 six months after the second dose. Result(s): 195 cancer pts: median age 64.1 y (Q1-Q3 53.8- 72.0);female 138 (70.8%);E-group (12.6%);active therapy 144 (86.7%);advanced stage of disease 131 (67.2%);breast cancer 100 (51.3%);chemotherapy 65 (33.3%), targeted therapy 69 (35.4%);multiple comorbidities 44 (22.6%);prophylaxis with G-CSF 15 (7.7%). 20 healthy subjects were enrolled as controls: median age 28.5 y (Q1-Q3 25.0-42.0), female 11 (55.0%). SR in nonEgroup was lower than in healthy controls (66.7% vs 95.0%, p=0.0085). Conversely, SR in E-group was comparable to healthy controls (93.3%, p=0.0020). In cancer pts, multiple comorbidities (p=0.0274) and the use of G-CSF (p=0.0151) negatively correlated with SR;mRNA-1273 induced a higher SR (p<0.0001). Clinical efficacy in pts was 97.4%. 7 pts were diagnosed for SARS-CoV-2 infection and confirmed by a RNA test. 5 pts developed COVID-19: 3 of them did not seroconvert at T1. COVID-19 disease was mild and managed at home. Only 1 hospitalization was recorded, but no ventilation or no intensive care admission was required. Conclusion(s): In our study, cancer pts with a previous SARS-CoV-2 infection showed a higher SR, similar to the one observed in healthy people. Besides, the presence of comorbidities and the use of G-CSF negatively affected the SR, while mRNA-1273 induced a higher SR. Interestingly, no COVID-19 serious complication or death were observed in all subgroups. Finally, as the third dose is the actual standard, identification of persistent non-responder pts is critical in order to select who could benefit of new treatments as monoclonal antibodies.
ABSTRACT
Background: Despite of the administration of multiple doses of vaccines (vax), cancer patients (pts) are a group at high risk of COVID-19 complications. The aim of this study is to evaluate the factors associated with the humoral response to the 3rd dose (D) of mRNA-based vax in cancer pts during or after active treatment. Patients and Methods: Single institution, prospective study conducted at the L. Sacco Hospital, Milan, between 5/2021-4/2022. 30 days after the 2nd and 30 days after the 3rdD of BNT162b2 or mRNA-1273 (selected based on local pharmacy availability), seric levels of 3 antibodies (Ab) were measured in solid tumors pts during or after the active treatment, by a fluorescence bead-based assay. Anti-S and anti-RBD IgG to determine the humoral response to vax, anti-N IgG to identify a previous exposure to SARS-Cov-2. Primary objective: to assess the seroconversion (SC) rate and the Ab titres after 3rdD. Secondary Objectives: to detect any relation between the 3rdD response and pre-defined pts variables;to evaluate the humoral response to 3rdD in pts not responding to the 2ndD. Result(s): 99 of 110 pts were evaluated: 67.7% female, median age 63 ys, 49.5% breast cancer, 67.7% advanced stage. Active treatment: 40.4% biologic agent, 23% chemotherapy (alone or combination), 11.1% hormone. 3rdD vax type: 74.8% BNT162b2, 25.2% mRNA-1273. SC after 3rdD was obtained in 99% of pts. The use of GCSF was associated with a lower amount of anti-RBD IgG (p=0.03). A 6 vs 5 months interval between 2nd and 3rdD was correlated with higher anti-S IgG level (p<0.001). The heterologous vax regimen was associated with higher rate of anti-S IgG (p=0.04), especially the sequence mRNA- 1273 x 2 -> BNT162b2 (p=0.001). No significant correlation at the multivariate analyses was found between Ab levels and the other variables tested (age, BMI, cancer type, tumor stage, use of steroids, previous exposure to SARS-CoV-2, anti-cancer therapy, neutropenic potential of the therapy). 21/22 pts not responding to the 2ndD obtained SC after 3rdD. Conclusion(s): 3rdD of anti-COVID-19 vax is effective in cancer pts with solid tumors undergoing or after recent treatment. In this group the 3rdD oversteps all the negative influence of the factors related to the 2ndD vax failure, achieving the same response of the healthy population and demonstrating efficacy in not previously responders, too. The better performance of the heterologous vax regimen could be due to an exposition to a wider range of epitopes.