Waning Long Term Efficacy of COVID-19 Post-Transplant Vaccination for Prevention of COVID-19 Adverse Events in Transplant and Cellular Therapy (TCT) Patients
Authors: Ramaswamy Rahul , Fakhoury Laith , Zhao Peter , Wu Ningying , Gao Feng , Uy Geoffrey L. , DiPersio John F. , Crees Zachary D. 
Published: December 2024

Coronavirus Disease 2019 (COVID-19) presents an increased risk to the transplant and cellular therapy (TCT) population, as it is associated with an increased incidence of severe infection, ICU admission, and COVID-19 attributable mortality as high as 20-30%. The TCT population also have diminished responses to vaccination, with ~60% seroconversion rate to COVID-19 vaccination during the 1st year post-TCT and &lt;50% of patients at a median of 92 months post-transplant generating recognizable T-cell responses to a single COVID-19 vaccination. The CDC and ASCO guidelines for severely immunocompromised patients recommend repeat COVID-19 vaccination with primary series followed by booster vaccination starting as early as 3 months following TCT. However, there remains a paucity of data regarding the clinical impact of post-TCT re-vaccination and with the development of emerging COVID-19 variants, there is a need for ongoing assessment of post-TCT COVID-19 re-vaccination efficacy.

This study is a single-center, retrospective study evaluating all adult patients who have received either hematopoietic cell transplantation (HCT) or CAR-T cell therapy at Washington University School of Medicine between January 1, 2021, and September 26, 2023. Per guideline recommendations and institutional policy, all patients post-TCT were offered COVID-19 vaccination and bivalent booster, as well as tixagevimab-cilgavimab (Evusheld) during the period it was available under FDA emergency authorization. All clinical variables were manually abstracted from the medical record and verified, including post-TCT COVID-19 vaccination status, Evusheld status, COVID-19 infection rate, receipt of COVID-19 directed therapies, and COVID-19 associated hospitalization/ICU admission/mortality. Competing risk survival analyses were conducted to evaluate the efficacy of post-transplant re-vaccination and Evusheld administration in preventing COVID-19 related adverse events (AEs), defined as infection, hospitalization, ICU admission or death, with death for other reasons as competing events. Cumulative incidences (CI) of COVID-19 related AEs were estimated using Fine and Gray's sub-distribution method.

A total of 885 post-TCT patients were included: 52.8% receiving autologous HCT, 32.8% receiving allogeneic HCT, and 14.5% receiving CAR-T cell therapy. Between the three treatment groups, the allogeneic HCT cohort had a greater incidence of COVID-19 related infections, hospitalizations, and ICU admissions irrespective of vaccination status. Cumulative incidence (CI) of COVID-19 related AEs in the post-TCT COVID-19 re-vaccinated group was 2% at 6 months and 9% at 12 months vs. 11% and 18% respectively in the unvaccinated group (p&lt;0.0001 at 6 months, p&lt;0.0001 at 12 months). However, by 18 months, there was no longer a significant difference in CI of COVID-19 related AEs between the two groups. Serious COVID-19 infection (defined as COVID-19 related hospitalization, ICU admission or death) occurred in 4.3% of the post-TCT re-vaccinated group vs. 7.1% of the unvaccinated group (p=0.0172). Among patients receiving Evusheld, CI of COVID-19 related AEs was 5% at 6 months and 10% at 12 months vs. 9% and 17% in those not receiving Evusheld, respectively (p=0.0264 at 6 months, p=0.0058 at 12 months). There was a 4.6% rate of serious COVID-19 infection in the Evusheld group vs. 6.8% rate in the non-Evusheld group, which was not statistically significant (p=0.2155).

In conclusion, post-TCT COVID-19 re-vaccination was associated with early reduction in COVID-19 related AEs at 6- and 12-months post-TCT, but these benefits were not sustained at 18 months post-TCT. COVID-19 re-vaccination post-TCT was also associated with reduction in severe COVID-19 infections leading to hospital admission, ICU stay or death. These findings highlight the impact of COVID-19 re-vaccination to reduce COVID-19 related AEs and serious COVID-19 infections in the first year post-TCT, but also demonstrate waning long term efficacy beyond 1-year post-TCT. Further research is needed to confirm these observations and to further elucidate the potential mechanisms for diminished long-term efficacy of COVID-19 vaccination in the post-TCT population.