C023 | UPDATED CLINICAL RESULTS: A MULTICENTER, OPEN-LABEL, PHASE 3 STUDY OF TABELECLEUCEL FOR SOLID ORGAN OR ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANT RECIPIENTS WITH EBV-DRIVEN POST-TRANSPLANT LYMPHOPROLIFERATIVE DISEASE AFTER FAILURE OF RITUXIMAB +

Background: The phase 3 ALLELE trial (NCT03394365) investigates tabelecleucel, an off-the-shelf allogeneic EBV-specific cytotoxic T-cell therapy, in patients with relapsed/refractory EBV+ post-transplant lymphoproliferative disease (R/R EBV+ PTLD) after solid organ (SOT) or hematopoietic stem cell transplant (HCT). Initial results from 43 patients were published; this update includes 75 patients. Methods: Patients received tabelecleucel (2×10⁶ cells/kg on days 1, 8, 15 in 35-day cycles). Efficacy and safety were assessed via independent oncologic response adjudication (IORA) using Lugano criteria with LYRIC modification. Key endpoints included overall response rate (ORR), duration of response (DOR), time to response (TTR), and overall survival (OS). Follow-up continued for up to 5 years. Results: At data cut-off (9 th October 2023), 75 pts (49 SOT, 26 HCT) were enrolled. Median time from transplant to EBV+PTLD diagnosis: SOT 0.9 years (0.2–26.2), HCT 3.9 mo (0.6–66.0). Prior therapies included rituximab monotherapy (86.7%), chemotherapy-containing regimens (46.7%), and rituximab+chemotherapy (37.3%). ORR: 50.7% (38/75; SOT 51.0% [25/49], HCT 50.0% [13/26]). TTR: 1.1 months (0.6–9.0). Complete response: 28.0% (21/75), partial response: 22.7% (17/75). Median DOR: 23.0 months (95% CI 12.1–NE); 20/38 responders lasted ≥6 months. Clinical benefit rate (CR, PR, or SD for ≥6 months): 60.0% (SOT 57.1%, HCT 65.4%). 1-year OS rate:55.7% (SOT 57.1%, HCT 52.4%); median OS: 18.4 months (SOT 18.4, HCT 18.6). Responders to tabelecleucel had a 1-year OS rate of 78.7% vs 28.2% for non-responders. Serious TEAEs: 65.4% HCT, 61.2% SOT; fatal TEAEs: 19.2% HCT, 18.4% SOT (none treatment-related). The safety profile was favorable and consistent with previous data. Conclusions: Updated ALLELE data confirm tabelecleucel's efficacy (ORR 50.7%, median DOR 23.0 months, OS 18.4 months) in R/R EBV+PTLD, in patients who otherwise have a median OS of 0.7-4.1 months in the absence of available treatment options. Safety remained favorable with no treatment-related fatalities or expected immune toxicities, supporting tabelecleucel as a potential new standard for this high-risk population.