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3532 Waning Long Term Efficacy of COVID-19 Post-Transplant Vaccination for Prevention of COVID-19 Adverse Events in Transplant and Cellular Therapy (TCT) Patients

Program: Oral and Poster Abstracts
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
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Rahul Ramaswamy, MD1*, Laith Fakhoury, BS1*, Peter Zhao, MD1*, Ningying Wu, MD, PhD2*, Feng Gao3*, Geoffrey L. Uy, MD4, John F. DiPersio, MD, PhD5 and Zachary D. Crees, MD5

1Washington University School of Medicine, St. Louis, MO
2Public Health Sciences Division, Washington University School of Medicine, St Louis, MO
3Department of Surgery, Division of Public Health Sciences, Washington University School of Medicine, Saint Louis, MO
4Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO
5Division of Oncology, Washington University School of Medicine, Saint Louis, MO

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 <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<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.

*signifies non-member of ASH