Long-Term Outcomes of Patients with Epstein-Barr Virus-Driven Post-Transplant Lymphoproliferative Disease Following Solid Organ Transplant or Allogeneic Hematopoietic Cell Transplant Treated with Tabelecleucel in a Multicenter Expanded Access Program Study

Background Patients (pts) undergoing a solid organ (SOT) or allogeneic hematopoietic cell transplant (HCT) are at risk for developing Epstein-Barr virus-driven post-transplant lymphoproliferative disease (EBV+PTLD). There is a need for effective and well-tolerated therapies in pts with EBV+PTLD who have failed rituximab ± chemotherapy (CT). Tabelecleucel (tab-cel) is an investigational, off-the-shelf, allogeneic EBV-specific T-cell immunotherapy generated from healthy donors that is selected for a given pt from an existing library, based on human leukocyte antigen (HLA) restriction and matching. Objective Here, we report long-term outcomes using tab-cel through an ongoing US, multicenter Expanded Access Program (EAP) study (EBV-CTL-201, NCT02822495) in pts with relapsed/refractory (R/R) EBV+PTLD following HCT (n = 14) and SOT (n = 12). Methods Pts received tab-cel matched by ≥2/10 HLA alleles, including ≥1 HLA allele through which tab-cel exerts cytotoxicity (HLA restriction). In each 5-week cycle, pts received tab-cel 1.6–2 × 106 cells/kg intravenously on days 1, 8, and 15, with an imaging-based response assessment around day 28. Pts were treated until maximal response (with up to 4 tab-cel restrictions), unacceptable toxicity, or withdrawal of consent. Results herein reflect a data snapshot from June 3, 2019. Results All pts had received prior rituximab and 7/12 SOT pts received prior CT. Intermediate/high risk PTLD-prognostic index (PTLD-IPI; Choquet et al, Ann Hematol 2007) was noted in 79% and 42% of HCT and SOT pts, respectively. The results are presented in figure 1. While the median follow-up time in HCT pts was short, 3 pts were followed for over 12 months including 2 who were followed for more than 24 months. In pts responding to tab-cel, 1-year OS was 85.7% in HCT and 100% in SOT, and no deaths were attributable to EBV+PTLD progression. In a subset of study pts (HCT: n = 11; SOT: n = 11) with adequate ECOG, no CNS disease, and no PTLD-related ventilatory support who would have likely been eligible for Atara's ongoing Phase 3 studies, the ORR was 55% (HCT) and 82% (SOT), with a 2-yr OS of 79% (HCT) and 81% (SOT). The safety profile of tab-cel was consistent with previously published data. At the data snapshot for this abstract, no tab-cel-related adverse events led to treatment discontinuation or death. In addition, no cytokine release syndrome, organ rejection or tumor flare adverse events were reported in the EBV+PTLD pts treated with tab-cel in this EAP study. Conclusions The data demonstrate a high response rate for tab-cel in EBV+PTLD in both HCT and SOT after initial treatment failure. Longer term follow-up shows a favorable 2-year OS in this predominantly high-risk population for whom there are no approved alternative therapies. Similar outcomes were observed in the subset of pts potentially eligible for ongoing Phase 3 studies of tab-cel in R/R EBV+PTLD following SOT or HCT.