Clinical Experience of Tabelecleucel in Epstein–Barr Virus-Positive Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) Involving the Central Nervous System

Background Tabelecleucel is an investigational, off-the-shelf, allogeneic EBV-specific T-cell immunotherapy being studied in patients (pts) with EBV+ diseases, including EBV+ PTLD with central nervous system (CNS) involvement. Pts with relapsed/refractory (R/R) EBV+ CNS PTLD have very limited treatment options and poor prognosis. We previously reported results from pts with R/R EBV+ CNS PTLD treated within 2 single-center studies. We report here a combined analysis from 4 open-label studies. Methods Safety and efficacy were evaluated using data from 4 open-label studies: 2 single-center, phase 2 (P2) trials (NCT00002663, n=10; NCT01498484, n=2), a multicenter, expanded-access protocol (EAP-201 [2016-2020]; NCT02822495, n=2) and the multicenter, P2 EBVision (study 205) trial (NCT04554914, n=4). Pts with R/R or treatment naïve EBV+ CNS PTLD received cycles of 3 weekly infusions of tabelecleucel at ∼2 × 106 cells/kg. Response was assessed by study investigator. Key endpoints were objective response rate (ORR), overall survival (OS), and safety parameters. Results Eighteen pts were included in this pooled analysis. Pts received a median (range) of 1 (0 to 5) lines of prior therapy. In all pts, ORR was 77.8% (95% CI: 52.4, 93.6), 1 yr and 2 yr OS rates were 70.6% and 54.9%, respectively (Table). There were no treatment-related fatal or life-threatening treatment-emergent adverse events (TEAEs) reported or serious treatment-related TEAEs of neurotoxicity, organ rejection, graft-versus-host disease, or tumor flare reaction of any grade. Conclusions In this combined analysis that includes the 1st reported EBVision data, tabelecleucel induced a high response rate of ∼78% and demonstrated promising survival among pts with EBV+ CNS PTLD, consistent with previous single-center experience. Tabelecleucel was also well tolerated. The P2 EBVision trial is ongoing to further investigate the clinical benefit of tabelecleucel in pts with EBV+ diseases.