Antiviral cellular therapy for enhancing T-cell reconstitution before or after hematopoietic stem cell transplantation (ACES): a two-arm, open label phase II interventional trial of pediatric patients with risk factor assessment.
Publication Year:
2024
PubMed ID:
38637498
Funding Grants:
Public Summary:
Viral infections are a common and potentially fatal complication in patients undergoing bone marrow transplant for treatment of cancer or immunodeficiency disorders. We utilized T cell therapy targeting 3 common viruses (cytomegalovirus, Epstein-Barr Virus, and adenovirus) to treat refractory viral infections in immunocompromised pediatric patients in a phase II, multi center study. A total of 51 patients were treated with virus-specific T cell therapy from an established bank. Overall, 62% of patients who were evaluable after bone marrow transplantation had a clinical response. T cell infusions were generally well tolerated, with rare serious adverse events, including loss of the bone marrow graft in 1 patient. Patients with certain conditions including graft-versus-host disease or transplant-associated thrombotic microangiopathy or those receiving immunosuppressive therapy were less likely to respond to VST therapy.
Scientific Abstract:
Viral infections remain a major risk in immunocompromised pediatric patients, and virus-specific T cell (VST) therapy has been successful for treatment of refractory viral infections in prior studies. We performed a phase II multicenter study (NCT03475212) for the treatment of pediatric patients with inborn errors of immunity and/or post allogeneic hematopoietic stem cell transplant with refractory viral infections using partially-HLA matched VSTs targeting cytomegalovirus, Epstein-Barr virus, or adenovirus. Primary endpoints were feasibility, safety, and clinical responses (>1 log reduction in viremia at 28 days). Secondary endpoints were reconstitution of antiviral immunity and persistence of the infused VSTs. Suitable VST products were identified for 75 of 77 clinical queries. Clinical responses were achieved in 29 of 47 (62%) of patients post-HSCT including 73% of patients evaluable at 1-month post-infusion, meeting the primary efficacy endpoint (>52%). Secondary graft rejection occurred in one child following VST infusion as described in a companion article. Corticosteroids, graft-versus-host disease, transplant-associated thrombotic microangiopathy, and eculizumab treatment correlated with poor response, while uptrending absolute lymphocyte and CD8 T cell counts correlated with good response. This study highlights key clinical factors that impact response to VSTs and demonstrates the feasibility and efficacy of this therapy in pediatric HSCT.
