Humoral Responses to Repetitive Doses of COVID-19 mRNA Vaccines in Patients with CAR-T-Cell Therapy

SIMPLE SUMMARY: Data on the efficacy of SARS-CoV-2 mRNA vaccinations in patients with CAR-T-cell therapy is very limited. We analyzed patients (predominantly DLBCL) undergoing CAR-T-cell therapy and receiving BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccination. This single center retrospective analysis aimed to evaluate the number of B-cells and CAR-T-cell copies as prognostic factors of humoral antibody test results as well as the effects of a third and fourth dose on humoral antibody response. Our results demonstrate that patients with more B-cells and fewer CAR-T-cells at vaccination were more likely to produce a positive antibody test result. Overall, we found very poor humoral antibody responses, while additional doses increased rates of seroconversion and antibody titers. ABSTRACT: Background: Due to B-cell aplasia following CAR-T-cell therapy, patients are at risk of severe SARS-CoV-2 course. Methods: COVID-19 vaccines were assessed by IgG antibody tests against SARS-CoV-2 spike protein (anti-S1/S2). Vaccination procedures: group (1): CAR-T-cells followed by two to four vaccine doses; group (2): Two vaccine doses prior to CAR-T-cells, followed by doses 3 or 4. Results: In group 1 (n = 32), 7/30 patients (23.2%) had positive antibody tests after a second dose, 9/23 (39.1%) after a third dose, and 3/3 patients after a fourth dose. A third dose led to seroconversion in 5 of 21 patients (23.8%) with available data, while a fourth dose did so in 2/3 patients. Higher B-cells (AUC: 96.2%, CI: 89–100, p = 0.0006) and lower CAR-T-cell copies (AUC: 77.3%, CI: 57–97, p = 0.0438) were predictive of positive humoral vaccine response. In group 2 (n = 14), 6/14 patients (42.9%) had a positive antibody test after a second dose, 3/8 patients (37.5%) after a third dose, and 3/4 patients after a fourth dose. A third dose led to seroconversion in 1/8 patients (12.5%), while a fourth dose did so in 3/4 patients. Conclusion: Additional vaccine doses increased seroconversion rates whilst high B-cell counts and low CAR-T-cell copy numbers were associated with positive antibody response.