Immunogenicity and Clinical Efficacy of Two Doses of Mrna-Based Covid-19 Vaccines for Patients with Solid Tumors on Active Anti-Cancer Treatment

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.