Efficacy and Safety of ATA129, Partially Matched Allogeneic Third-Party Epstein-Barr Virus-Targeted Cytotoxic T Lymphocytes in a Multicenter Study for Post-Transplant Lymphoproliferative Disorder

Post-Transplant Lymphoproliferative Disorder (PTLD), an EBV-driven lymphoproliferative disorder (LPD), represents a life-threatening challenge for patients (pts) following solid organ transplant (SOT) or hematopoietic cell transplant (HCT). Though some pts will respond to reduction of immunosuppression or rituximab therapy, failure of rituximab-based 1st line therapy predicts a dismal prognosis in post-HCT PTLD pts with a median overall survival (OS) of 16-56 days. In SOT-associated PTLD, pts failing rituximab experience increased chemotherapy-induced treatment-related mortality compared to other lymphoma pts. EBV-CTLs have previously been shown to induce durable responses in pts with SOT- or HCT-associated PTLD despite rituximab failure. Here we report interim study results for using ATA129, an allogeneic off-the-shelf EBV-CTL cell product derived from volunteer donors, for pts with HCT- or SOT-associated PTLD treated on EBV CTL 201, a multicenter expanded access protocol (EAP) for pts with EBV-driven diseases.

Methods: Eligible pts were those with EBV+ PTLD, other EBV-driven malignancies, EBV+ hemophagocytic lymphohistiocytosis (HLH), or EBV viremia; adequate organ function; adequate performance status; and measurable disease who provided informed consent. Enrollment is ongoing. Pts are treated with partially HLA-matched ATA129 sharing ≥2 HLA alleles with the pt, at least one of which is an HLA allele through which ATA129 exerts cytotoxicity (referred to as HLA restriction). The dose of ATA129 is 1.6-2 x 10^6 cells/kg on days 1, 8, and 15 of every 35d cycle. Pts undergo radiographic, biochemical (HLH), or virologic assessment at ~day 28 of each cycle Pts with progressive disease after 1 cycle may undergo Switch Therapy to an ATA129 product with a different HLA restriction. Objective response rate (ORR) is determined radiographically and represents the best response observed across all ATA129 lots received for any given pt.

Results: Ten PTLD pts received ATA129 and have sufficient follow-up to assess response (efficacy population): 5 PTLD pts post-HCT; 5 PTLD pts post-SOT. For SOT-PTLD, the objective response rate (ORR) is 100%; for HCT-PTLD, the ORR is 80%. An additional 2 PTLD pts have received ATA129 but are too early to assess. For these 12 PTLD pts, median age was 27 (range 7-58); median number of ATA129 cycles was 2 (range 1-8); median follow-up was 3.3 months (range 1-12 months) and median number of ATA129 cell product lots per pt was 1 (range 1 - 5). An additional 10 pts with various non-PTLD EBV+ diagnoses are included in the safety population only. Treatment-related treatment-emergent serious AEs have been reported in 5 of the 22 treated pts (2 PTLD and 3 non-PTLD pts). However, in this generally ill population, the only safety signal observed was tumor flare in 1 patient.

Conclusions: ATA129 provided a high response rate in the PTLD population (80-100%) in the multicenter EAP EBV-CTL-201, consistent with prior reports for single institution studies. A low number of related SAEs was observed across different diagnoses on EBV-CTL-201. Updated safety and efficacy data will be presented at the meeting.