T-Cell Immunotherapy for Posttransplant EBV-Positive Lymphoma

Epstein–Barr virus (EBV)–positive posttransplant lymphoproliferative disorder (PTLD) is a well-recognized complication of hematopoietic stem-cell transplantation (HSCT) and solid organ transplantation (SOT). Patients who do not respond to a decrease in immunosuppressive therapy, rituximab, or rituximab plus chemotherapy have a very poor prognosis. Investigators now report updated safety and efficacy findings from a phase 3, single-arm, open-label, multicenter, industry-sponsored trial of tabelecleucel, an allogeneic EBV-specific T-cell immunotherapeutic, in patients with relapsed or refractory EBV-positive PTLD.

A dose of 2×10⁶ cells/kg was administered intravenously on days 1, 8, and 15 in 35-day cycles, followed by observation. Any nonresponders could be retreated with tabelecleucel using a T-cell line with a different human leukocyte antigen (HLA) restriction. Treatment ended with achievement of maximal response, intolerable toxicity, start of nonprotocol therapy, or failure of tabelecleucel with up to four (for HSCT) or two (for SOT) different HLA restrictions.

Of 63 patients assessed for eligibility for participation, 43 were included in the trial. Among these 43 patients, an objective response (primary endpoint) was achieved in 7/14 (50%) in the HSCT patient group, with a median follow-up of 14.1 months, and in 15/29 (52%) in the SOT group, with a median follow-up of 6 months. Nine patients progressed on treatment. There was no evidence of cytokine release syndrome, tumor flare, or neurotoxicity syndrome as is seen with autologous chimeric antigen receptor (CAR) T-cell agents; no fatal treatment-related adverse events were reported. One patient developed grade 1 chronic graft-versus-host disease.