SARS-CoV-2-reactive antibody waning, booster effect and breakthrough SARS-CoV-2 infection in hematopoietic stem cell transplant and cell therapy recipients at one year after vaccination

Abstract

The kinetics of SARS-CoV-2 reactive IgG antibodies after full vaccination and booster in allogeneic and autologous stem cell transplantation (allo-HSCT, ASCT) and chimeric antigen receptor T-cell therapy (CAR-T) are of utmost importance for estimating risk of infection. A prospective multicenter registry-based cohort study, conducted from December 2020 to July 2022 was used to analyze antibody waning over time, booster effect and the relationship of antibody response and breakthrough infection in 572 recipients (429 allo-HSCT, 121 ASCT and 22 CAR-T cell therapy). A significant decline in antibody titers was observed at 3 and 6 months after full vaccination in recipients without pre-vaccine SARS-CoV-2 infection, whereas recipients infected prior to vaccination showed higher and stable antibody titers over time. In poor responders, a booster dose was able to increase antibody titers in 83% of allo-HSCT and 58% of ASCT recipients but not in CART-T cell recipients [0%] (p < 0.01). One-year cumulative incidence of breakthrough infection was 15%, similar among cell therapy procedures. Immunosuppressive drugs at the time of vaccination [hazard ratio (HR) 1.81, p = 0.0028] and reduced intensity conditioning (HR 0.49, p = 0.011) were identified as the only conditions associated with different risk of breakthrough infection in allo-HSCT recipients. Antibody titers were associated with breakthrough infection and disease severity. No death was observed among the 72 breakthrough infections. Antibody level decay after the first two vaccine doses was common except in recipients with pre-vaccination SARS-CoV-2 infection. Poorly responding allo-HSCT recipients showed a response advantage with the booster as compared to ASCT and, especially, the null response found in CAR-T cell recipients. Antibody titers were positively correlated with the risk of breakthrough SARS-CoV-2 infection which was mainly driven by the immunosuppression status.

Fig. 1. Antibody titers kinetics.

Antibody titers in BAU/mL at at 3-6 weeks, 3 months and 6 months after complete vaccination and after booster dose a in allo-HSCT, b according to donor type and c in ASCT recipients. a Abbreviations, Q3-med means median interquartil 75%; Med-Q1, median interquartil 25%. * median test p value <0.05. ** median test p value not significant. b Abbreviations, Q3-med means median interquartil 75%; Med-Q1, median interquartil 25%. * median test p value <0.05. ** median test p value not significant. (see Suplementary Table S3 of Fig. 1b). C) Abbreviations, Q3-med means median interquartil 75%; Med-Q1, median interquartil 25%. * median test p value <0.05. ** median test p value not significant. (see Suplementary Table S4 of Fig. 1c).

Fig. 2. Antibody kinetics in CAR-T cell recipients at different time points and after booster.

Antibody levels increased significantly after booster vaccine dose (P < 0.05 for all comparisons, median test).

Fig. 3. Cumulative incidence of breakthrough SARS-CoV-2 infection.

Cumulative incidence of SARS-CoV-2 infection in allo-HSCT according to a cell therapy procedure, b use of immunosuppression at the time of first vaccine dose and c conditioning intensity.