Final Outcomes From a Phase 2 Trial of Posoleucel in Allogeneic Hematopoietic Cell Transplant Recipients

Authors

Sanjeet S Dadwal
Rajat Bansal
Michael W Schuster
Jean A Yared
Gary Douglas Myers
Michelle Matzko
Sama Adnan
David McNeel
Julie Ma
Sarah A Gilmore
Spyridoula Vasileiou
Ann M Leen
Joshua A Hill
Jo-Anne H Young

Language

English

Publication Date

9-10-2024

Journal

Blood Advances

DOI

10.1182/bloodadvances.2023011562

PMID

38593233

PMCID

PMC11413696

PubMedCentral® Posted Date

4-10-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Allogeneic hematopoietic cell transplantation (allo-HCT) recipients are susceptible to viral infections. We conducted a phase 2 trial evaluating the safety and rate of clinically significant infections (CSIs; viremia requiring treatment or end-organ disease) after infusion of posoleucel, a partially HLA-matched, allogeneic, off-the-shelf, multivirus-specific T-cell investigational product for preventing CSIs with adenovirus, BK virus, cytomegalovirus, Epstein-Barr virus, human herpesvirus-6, or JC virus. This open-label trial enrolled allo-HCT recipients at high risk based on receiving grafts from umbilical cord blood, haploidentical, mismatched, or matched unrelated donors; post-HCT lymphocytes of < 180/mm3; or use of T-cell depletion. Posoleucel dosing was initiated within 15 to 49 days of allo-HCT and subsequently every 14 days for up to 7 doses. The primary end point was the number of CSIs due to the 6 target viruses by week 14. Of the 26 patients enrolled, only 3 (12%) had a CSI by week 14, each with a single target virus. In vivo expansion of functional virus-specific T cells detected via interferon-γ enzyme-linked immunosorbent spot assay was associated with viral control. Persistence of posoleucel-derived T-cell clones for up to 14 weeks after the last infusion was confirmed by T-cell–receptor deep sequencing. Five patients (19%) had acute graft-versus-host disease grade 2 to 4. No patient experienced cytokine release syndrome. All 6 deaths were due to relapse or disease progression. allo-HCT recipients at high risk who received posoleucel had low rates of CSIs from 6 targeted viruses. Repeat posoleucel dosing was generally safe and well tolerated and associated with functional immune reconstitution.

Keywords

Adult, Aged, Female, Humans, Male, Middle Aged, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Transplantation, Homologous, Treatment Outcome, Virus Diseases, Transplant Recipients, Cell- and Tissue-Based Therapy

Comments

This trial was registered at www.ClinicalTrials.gov as #NCT04693637.

Published Open-Access

yes

Recommended Citation

Dadwal, Sanjeet S; Bansal, Rajat; Schuster, Michael W; et al., "Final Outcomes From a Phase 2 Trial of Posoleucel in Allogeneic Hematopoietic Cell Transplant Recipients" (2024). Faculty and Staff Publications. 4990.
https://digitalcommons.library.tmc.edu/baylor_docs/4990