Donor-derived T cells that target proteins of the Epstein-Barr virus (EBV) in relapsed or refractory lymphoma can improve overall survival in the adjuvant setting, according to research from a small study that was recently published in Blood.1
The experimental T cells were infused into 26 patients, who received an allogeneic bone marrow transplant for EBV-associated lymphomas. Seven patients had active disease at the time of infusion, while 19 received the T cells after transplant as adjuvant therapy for high-risk disease.
“These patients were the sickest of the sick,” having exhausted other treatment options, said Catherine M. Bollard, MD, the principal investigator, who began the phase 1 clinical trial at Baylor College of Medicine in Houston, Texas, before opening a tandem trial at Children’s National in Washington, District of Columbia.
Those who had the best outcome after T-cell therapy had B-cell diseases, a finding investigators attributed, in part, to B cells’ antigen-presenting role in the body, Dr Bollard said.Two-year overall survival reached 80%, which is 12% higher than the patient group as a whole.
Infection with the EBV virus has been linked to a number of cancers, including over 90% of nasopharyngeal cancers, up to 40% of Hodgkin lymphoma, and 20% of diffuse large B-cell lymphoma, among others.2
Researchers have identified at least 9 EBV proteins, along with different phases of protein expression during the virus’ latent or dormant period. Type III latency, in which tumors express all 9 membrane proteins, are considered the most immunogenic and the most amenable to EBV-directed T-cell therapies, Dr Bollard said. Although the type II latency tumors treated in the current study were less immunogenic, targeting them prevented relapse in high-risk patients (after transplant) without significant toxicity.
In the study, patients with active disease at the time of T-cell infusion fared poorly compared with patients receiving adjuvant therapy, explained Dr Bollard. But, these patients still did slightly better than expected, given a less than 20% chance for a good outcome if relapse occurs following transplant.
In general, patients with T-cell-mediated lymphoma also did better than expected. Two-year overall survival in this group reached 60%, compared with previously published 2-year posttransplant survival rates of approximately 30%.
How soon EBV-specific T-cell therapies might be licensed is uncertain and is awaiting further study.