Virus-Specific T-Cell Therapy Effective for Viral Infections After Hematopoietic Stem Cell Transplantation

Use of virus-specific T cells (VST) from a cell bank appeared safe and effective for patients with viral infections following allogeneic stem cell transplantation (HSCT), according to phase 1 trial results presented at the 61st American Society of Hematology (ASH) Annual Meeting & Exposition, held in Orlando, Florida.

In this study, researchers used cryopreserved, third-party, partially human leukocyte antigen-matched VST cells developed against cytomegalovirus (CMV), Epstein-Barr virus (EBV), or adenovirus (ADV). Patients who had undergone HSCT received a maximum of 4 doses beginning within a week of initial antiviral therapy for a reactivated virus. HSCT involved matched-unrelated donors for 20 patients, and 21 patients had undergone T-cell depletion.

Among 188 VST doses produced in this study, the median virus specificities were highest for EBV (83%) and CMV (75%), and lower for ADV (37%). Evaluable patients (N=25) received virus-specific T cells for CMV (22), EBV (2), or ADV (1). Most patients (18) were given 1 infusion of VST, but 6 patients received 2 infusions and 1 received 4 infusions.

The median follow-up time was 431 days after transplant. Complete viral clearance of the targeted infection was reported in 92% (23) of patients, and partial viral response was reported for 2 patients. Best viral response occurred at a median time of 20 days, and 80% (20) of patients had survived by follow-up. The 1-year nonrelapse mortality rate was reportedly 12%.

Mild adverse events related to infusions were reported in 3 patients. Chronic graft-versus-host disease (GVHD) developed in 3 patients. Acute GVHD accounted for 2 postinfusion fatalities, and 2 patients developed new-onset GVHD of grade 1 postinfusion.

The investigators concluded that for recipients of HSCT, treatment of CMV, EBV, or ADV with viral-specific T cells as administered in this study was associated with high rates of complete viral clearance and overall survival, while demonstrating low rates of toxicity.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original abstract for a full list of disclosures.

Reference

Gottlieb D, Jiang W, Avdic S, et al. Administration of third-party virus-specific T-cells (VST) at the time of initial therapy for infection after haemopoietic stem cell transplant is safe and associated with favourable clinical outcomes (the R3ACT-Quickly trial). Oral presentation at: 61st ASH Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 251.