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3462 CMV-Specific TCR-T Cells for the Treatment of CMV Reactivation after Allogeneic Hematopoietic Stem-Cell Transplantation

Program: Oral and Poster Abstracts
Session: 704. Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical trials, Clinical Research
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Jingwen Tang, MS1*, Liping Dou, MD2 and Daihong Liu, MD2*

1Medical School of Chinese PLA, Beijing, China
2Department of Hematology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China

Cytomegalovirus (CMV) reactivation remains the leading cause of death after haploidentical stem cell transplantation (HSCT). Current therapies, including antiviral drugs and relay cell therapy using CMV-specific cytotoxic T lymphocytes (CTLs), have shown only limited benefit to patients, and T-cell receptor (TCR)-T-cell therapy offers a promising option for the treatment of CMV reactivation.

To evaluate the efficacy and safety of CMV-targeted T-cell receptor-engineered T (CMV-TCR-T) cell therapy as a first-line pre-emptive therapy ,we conducted a single-arm, open-label, phase I clinical trial for patients with CMV reactivation after HSCT. Ten patients with CMV reactivation after HSCT were adoptively transferred by one to three doses of HSCT donors-derived CMV-TCR-T cells. Meanwhile, 2 patients who had failed standard antiviral drugs used CMV-TCR-T cells as second-line therapy.

Eight of the first-line treatment patients responded within one month after infusion of CMV-TCR-T cells without administration of any antiviral drugs; the other two patients who initially did not respond to CMV-TCR-T cell therapy were given salvage ganciclovir and phosphonate, followed by rapid clearance of CMV. Second-line treatment patients were controlled with TCR-T cells after 2 weeks of ineffective use of antiviral drugs. CMV-TCR-T cells demonstrated overall robust expansion and persistence in peripheral blood after infusion. CMV-TCR-T cells were first detected in the peripheral blood of these patients 3-7 days after the initial CMV-TCR-T infusion, expanded rapidly and persisted for at least 1-4 months, providing long-term protection against CMV reactivation. In 2 patients, CMV-TCR-T cells began to expand even while anti-graft-versus-host disease reagents were still in use, further demonstrating the proliferative potential of CMV-TCR-T cells. No adverse events were observed except for grade 1 cytokine release syndrome in one patient and mild fever in two patients.

Median follow-up was 318 days. Six patients survived for more than 1 year and 2 patients died (2 in the first-line treatment group and 1 in the second-line treatment group).This study demonstrates the great potential of CMV infection after HSCT or other organ transplantation in terms of treatment and prevention.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH