Poor humoral responses to mRNA vaccines against SARS-CoV-2 in patients after CAR-T-cell therapy

ABSTRACT

Introduction: Immunosuppressed patients are at risk of a severe SARS-CoV-2 course. Patients after CAR-T-cell therapy inevitably have B-cell aplasia and are particularly vulnerable. Data on efficacy and optimal sequence of SARS-CoV-2 vaccination in CAR-T-cell recipients are missing. Methods: We analyzed all consecutive alive patients (predominantly DLBCL) undergoing CAR-T-cell therapy between 01/2019-08/2021. Patients received two Covid-19 mRNA vaccines between 01/2021-08/2021. We assessed the efficacy of the vaccines using IgG antibodies against SARS-CoV-2 spike protein (anti-S1/S2) (Clia Diasorin;cut-off >12 AU/ml) and separated patients into two groups 1) CAR-T-cell infusion pre-vaccination;2) CAR-T cell infusion post-vaccination. Results: We identified 44 patients vaccinated with mRNA-1273 (Moderna) (33 pts;75%) or BNT162b2 (Pfizer-BioNTech) (11 pts;25%). In group 1 (28 pts), only 21% had positive antibodies after two vaccine doses while in group 2 (16 pts), 31% did so. In group 1, higher B-cell numbers (>22/μ l B-cells;PPV 83,3%;NPV 100%) and lower CAR-T-cell copy numbers (<50/μ g DNA CAR-T-cell copies;PPV 57.1%, NPV 94.4%) were predictive of positive humoral vaccine response. Patients without detectable B-cells when vaccinated produced negative antibody tests. In group 2, positive anti-spike protein IgG-antibodies after CAR-T-cell therapy declined by a median of 73.8 AU/ml at two consecutive assessments after a median of 74 days. Conclusion: Our results suggest poor humoral antibody responses in patients with prior CAR-T-cell therapy after mRNA Covid-19 vaccines. Low B-cell counts are associated with high CAR-T-cell copy numbers at vaccination and lacking antibody response. Anti-spike protein IgG values significantly declined in patients vaccinated before CAR-T-cell therapy.