ABSTRACT
Background: Since the beginning of the covid19 pandemic, clinical and demographic data showed that cancer patients are at high risk of developing severe consequences of Sars-Cov2 disease. For this reason, vaccination is strongly recommended, especially for patients on active treatment. Nevertheless, the efficacy of the Sars-Cov2 vaccine in cancer patients is not fully investigated. Our trial aim to explore the seroconversion in a large series of vaccinated cancer patients undergoing active treatment. Here we present a subgroup analysis concerning patients affected by breast cancer. Methods: The "VAX-on" is a single-center study that enrolled 366 cancer patients who underwent oncological treatment within the last six months. The study was approved by the ethics committee and all patients had to sign specific informed consent to be enrolled. Subjects were vaccinated against Sars-Cov2 with mRNA vaccine BNT162b2 (Comirnaty)-Pfizer BioNTech. Blood samples were obtained to quantify the production of specific anti-Spike IgG antibodies at day 21 from the first dose and at 6-8 weeks after the second dose. The antibody laboratory title cut-off of 50 U.A./mL defined the seroconversion. Results are shown as Mean and Standard Deviation for Scontinuous variable, percentage (%) for categorical ones. The Mann-Whitney test or Chi-Square test were used to compare continuous or categorical groups, respectively. Results: A total of 100 patients with breast cancer were enrolled. Clinical and demographic data are summarized in Table 1. The median age was 60.5 years and the majority had an ECOG PS of 0 (75%). Almost all were women (97%), with advanced cancer in 60% of cases. In early or advanced setting 46% patients were treated with chemotherapy while 54% were on target therapy (also including monoclonal antibody and CDK4/6 inhibitors). The mean antibody title after the first dose of mRNA Comirnaty vaccine was 2185.03±9303.26 U.A./mL (M±SD), while after the second dose the mean antibody title rise to 6492.10±10425.95 (M±SD). After the first dose 61% of patients were considered as immunized, meanwhile after the second dose 86% of patients resulted immunized (defined as an antibody title >50 U.A./mL). In the 9 patients in treatment with steroids (prednisone > 10mg/die or equivalent), there was a trend to a decreased antibody development compared to patients without chronic use of steroids (p 0.06 and 0.05 after the first and second dose, respectively). Of interest, patients using G-CSF (12%) had a significant reduction in the production of Sars-Cov2 antibody after vaccination compared to patients who did not use them (p 0.02 and <0.001 after the first and second dose, respectively), with only 75% resulted positively immunized after the second dose (p=0.04). No differences were seen when comparing patients in advanced with non-advanced stage. Conclusions: Our study demonstrated 86% seroconversion in cancer patients after the second dose of mRNA vaccine regardless of disease stage or type of cancer treatment received. Further evaluations are needed to define whether the use of corticosteroids and G-CSF have an impact on seroconversion.
Subject(s)
COVID-19 , Neoplasms , BNT162 Vaccine , Humans , Neoplasms/drug therapy , Neoplasms/genetics , RNA, Messenger/genetics , SARS-CoV-2ABSTRACT
BACKGROUND: Preliminary analysis from the Vax-On study did not find a correlation between cancer treatment type and antibody response to COVID-19 vaccination. We carried out a secondary subgroup analysis to verify the effects of comprehensive cancer treatment classification on vaccine immunogenicity. METHODS: The Vax-On study prospectively enrolled patients who started a two-dose messenger RNA-BNT162b2 vaccine schedule from 9 March 2021 to 12 April 2021 (timepoint-1). Those on active treatment within the previous 28 days accounted for the exposed cases. Patients who had discontinued such treatment by at least 28 days or received intravesical therapy represented the control cases. Quantification of immunoglobulin G (IgG) antibodies against the receptor binding domain of the S1 subunit of the SARS-CoV-2 spike protein was carried out before the second dose (timepoint-2) and 8 weeks thereafter (timepoint-3). Seroconversion response was defined at ≥50 arbitrary units/ml IgG titer. Classification of antineoplastic agents was based on their pharmacodynamic properties. RESULTS: Three hundred and sixty-six patients were enrolled (86 and 260 as control and exposed cases, respectively). Univariate analysis revealed a significantly lower IgG titer after both doses of vaccine in subgroups treated with tyrosine kinase inhibitors (TKIs), multiple cytotoxic agents, alkylating agents, and topoisomerase inhibitors. At timepoint-3, seroconversion response was significantly impaired in the topoisomerase inhibitors and mechanistic target of rapamycin (mTOR) inhibitors subgroups. After multivariate testing, treatment with alkylating agents and TKIs was significantly associated with a reduced change in IgG titer at timepoint-2. Treatment with mTOR inhibitors resulted in a similar interaction at each timepoint. Cyclin-dependent kinase 4/6 inhibitor treatment was independently correlated with an incremental variation in IgG titer at timepoint-3. Specific subgroups (TKIs, antimetabolites, alkylating agents, and multiple-agent chemotherapy) predicted lack of seroconversion at timepoint-2, but their effect was not retained at timepoint-3. Eastern Cooperative Oncology Group performance status 2, immunosuppressive corticosteroid dosing, and granulocyte colony-stimulating factor use were independently linked to lower IgG titer after either dose of vaccine. CONCLUSIONS: Drugs interfering with DNA synthesis, multiple-agent cytotoxic chemotherapy, TKIs, mTOR and cyclin-dependent kinase 4/6 inhibitors differentially modulate humoral response to messenger RNA-BNT162b2 vaccine.