Abstract
Background: Tabelecleucel is an off-the-shelf, allogenic Epstein-Barr virus (EBV)-specific cytotoxic T cell therapy for relapsed or refractory EBV-associated post-transplant lymphoproliferative disorders (R/R EBV+ PTLD). The efficacy and safety of tabelecleucel is being investigated in patients with R/R EBV+ PTLD after hematopoietic cell transplant (HCT) or solid organ transplant (SOT) in the ongoing multicenter, open-label phase 3 ALLELE trial (NCT03394365). Results from 26 HCT and 49 SOT patients were reported previously (Ghobadi et al. ASH 2024, Chaganti et al. ESOT 2025). Here we present updated results from a larger number of patients (29 HCT, 57 SOT) focusing on a subgroup analysis based on prior treatment.
Methods: Eligibility criteria required HCT patients to have failed prior treatment with rituximab, and SOT patients to have failed prior treatment with rituximab (SOT-R) or rituximab and chemotherapy (SOT-RC). Patients received intravenous tabelecleucel at 2 x 106 cells/kg on days 1, 8, and 15 in 35-day cycles. Clinical and radiographic assessments were conducted toward the end of each cycle and treatment response evaluated by independent oncologic response adjudication (IORA). After treatment, disease assessments were conducted up to 2 years and survival status up to 5 years. The primary objective was objective response rate (ORR), and secondary objectives included time to response (TTR) and overall survival (OS). Safety was assessed in all patients who received ≥1 dose of tabelecleucel.
Results: As of 10 September 2024, 29 HCT patients and 57 SOT patients (21 SOT-R, 36 SOT-RC) were enrolled and treated with tabelecleucel. The median (range) age was 42.6 (2.7-81.5) years, and 12 patients were <17 years of age. In patients ≥16 years of age, 48.7% were intermediate risk, and 43.4% were high risk at study entry per the PTLD-adapted prognostic index. The ORR for HCT was 48.3% (14/29 patients, 95% CI 29.4, 67.5) and for SOT was 47.4% (27/57 patients, 95% CI 34.0, 61.0). ORR for SOT-R was 52.4% (11/21 patients, 95% CI 29.8, 74.3) and for SOT-RC was 44.4% (16/36 patients, 95% CI 27.9, 61.9). For the 14 HCT treatment responders, the median (range) TTR was 1.0 (0.6-9.0) months and for the 27 SOT responders it was 2.1 (0.7-4.7) months. The median (95% CI) OS from Kaplan-Meier survival estimates for the HCT cohort was 18.6 (5.6-not estimable [NE]) months. For the SOT cohort, median OS was NE (9.0 months, NE) as more than half the patients remained in follow-up. For SOT-R, median OS was NE (5.5 months, NE) and for SOT-RC it was 21.6 months (5.0, NE). The estimated OS rate at 1 year (95% CI) for HCT was 54.3% (33.3, 71.2) and for SOT was 62.6% (48.0, 74.1). For HCT treatment responders, the 1-year OS rate (95% CI) was 71.4% (40.6, 88.2) while 2-year rate was 62.5% (31.5, 82.6). For SOT treatment responders, the 1-year OS rate was 88.1% (67.5, 96.0; 90.9% [50.8, 98.7] for SOT-R and 85.6% [53.3, 96.2] for SOT-RC), while the 2-year rate was 78.6% (55.6, 90.6).
Serious adverse events (SAEs) were reported in 17 HCT patients (58.6%) and 38 SOT patients (66.7%). These events were related to study treatment in 1 HCT patient (3.4%) and 7 SOT patients (12.3%). Fatal SAEs were reported in 5 HCT patients (17.2%) and 9 SOT patients (15.8%), none of which were related to treatment. SAEs of special interest were reported in 3 HCT patients (10.3%; 2 reported cases of GvHD, 1 chronic case of graft vs host disease, and 1 case of maculo-papular rash) and 1 SOT patient (1.8%; pyrexia). The case of pyrexia was deemed possibly related to the study treatment. Cases of transplant rejection were reported in 4 SOT patients (7.0%), though none were considered treatment-related. This updated tabelecleucel safety profile is consistent with results previously reported.
Conclusion: Results from the ALLELE trial continue to demonstrate the efficacy of tabelecleucel with an ORR of 48.3% in the HCT cohort and 47.4% in the SOT cohort. A favorable, but not a statistically significant ORR for SOT-R compared with SOT-RC was observed. Overall, these findings represent a novel treatment option for patients with R/R EBV+ PTLD who have poor survival and no alternative treatments available. The safety profile of tabelecleucel was favorable and no new safety concerns were identified.