Antineoplastic treatment class modulates COVID-19 mRNA-BNT162b2 vaccine immunogenicity in cancer patients: a secondary analysis of the prospective Vax-On study

ABSTRACT Background Preliminary analysis from Vax-On study did not find a correlation between cancer treatment type and antibody response to COVID-19 vaccination. We performed a secondary subgroup analysis to verify the effects of comprehensive cancer treatment classification on vaccine immunogenicity. Methods The Vax-On prospectively enrolled patients who started two-dose mRNA-BNT162b2 vaccine schedule from March 9 to April 12, 2021 (timepoint-1). Those on active treatment within 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 IgG antibodies against receptor binding domain of the S1 subunit of SARS-CoV-2 spike protein was performed before the second dose (timepoint-2) and 8 weeks thereafter (timepoint-3). Seroconversion response was defined at ≥50 AU/mL IgG titer. Classification of antineoplastic agents was based on their pharmacodynamic properties. Results 366 patients were enrolled (86 and 260 as control and exposed cases, respectively). Univariate analysis revealed significantly lower IgG titer after both doses of vaccine in subgroups treated with TKIs, multiple cytotoxic agents, alkylating agents, and topoisomerase inhibitors. At timepoint-3, seroconversion response was significantly impaired in topoisomerase inhibitors and mTOR inhibitor subgroup. After multivariate testing, treatment with alkylating agents and TKIs were significantly associated with reduced change in IgG titer at timepoint-2. Treatment with mTOR inhibitors resulted in a similar interaction at each timepoint. CDK4/6 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. ECOG-PS2, immunosuppressive corticosteroid dosing and G-CSF use independently linked to lower IgG titer after either dose of vaccine. Conclusions Drugs interfering with DNA synthesis, multiple-agent cytotoxic chemotherapy, TKIs, mTOR and CDK4/6 inhibitors differentially modulate humoral response to mRNA-BNT162b2 vaccine.