Session: 722. Allogeneic Transplantation: Acute and Chronic GVHD and Immune Reconstitution: Poster II
Hematology Disease Topics & Pathways:
Research, Adult, Clinical Research, Health outcomes research, Diseases, Immune Disorders, Immunodeficiency, SARS-CoV-2/COVID-19, Infectious Diseases, Human
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<0.0001 at 6 months, p<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.
Disclosures: DiPersio: WUGEN: Current equity holder in private company, Research Funding; Magenta Therapeutics: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; RiverVest Venture Partners: Consultancy, Membership on an entity's Board of Directors or advisory committees; SPARC: Consultancy; hC Bioscience, Inc.: Membership on an entity's Board of Directors or advisory committees; NeoImmune Tech: Research Funding; Vertex: Consultancy; Macrogenics: Research Funding; Bioline Rx: Research Funding. Crees: BioLineRx, Ltd.: Consultancy, Membership on an entity's Board of Directors or advisory committees.