Publication Date

1-17-2023

Journal

Clinical Cancer Research

DOI

10.1158/1078-0432.CCR-22-2415

PMID

36628536

PMCID

PMC9843433

PubMedCentral® Posted Date

1-11-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Adult, Child, Humans, Antiviral Agents, Cell- and Tissue-Based Therapy, Epstein-Barr Virus Infections, Hematopoietic Stem Cell Transplantation, Herpesvirus 4, Human, Virus Diseases

Abstract

PURPOSE: Viral infections are a major cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (allo-HCT). In the absence of safe and effective antiviral treatments, virus-specific T cells have emerged as a promising therapeutic option. Posoleucel is a multivirus-specific T-cell therapy for off-the-shelf use against six viral infections that commonly occur in allo-HCT recipients: adenovirus, BK virus (BKV), cytomegalovirus, Epstein-Barr virus, human herpes virus-6, and JC virus.

PATIENTS AND METHODS: We conducted an open-label, phase II trial to determine the feasibility and safety of posoleucel in allo-HCT recipients infected with one or more of these viruses. Infections were either unresponsive to or patients were unable to tolerate standard antiviral therapies. Fifty-eight adult and pediatric patients were enrolled and treated.

RESULTS: Posoleucel was well tolerated, with no cytokine release syndrome or other infusion-related toxicities; two patients (3.4%) developed Grade 2 and one patient (1.7%) Grade 3 GvHD during the trial. The overall response rate 6 weeks after the first posoleucel infusion was 95%, with a median plasma viral load reduction of 97%. Of the 12 patients who had two or more target viral infections identified at study entry, 10 (83%) had a clinical response for all evaluable viruses. Of the 23 patients treated for refractory BKV-associated hemorrhagic cystitis, 74% had resolution of symptoms and macroscopic hematuria by 6 weeks post-infusion.

CONCLUSIONS: In this open-label trial, treatment of refractory viral infections/disease in allo-HCT recipients with posoleucel was feasible, safe, and effective.

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