Subgroup analysis in pediatric patients from the Phase 3 study of tabelecleucel for allogeneic or solid organ transplant recipients with Epstein–Barr virus-driven post-transplant lymphoproliferative disease after failure of rituximab or rituximab and chemotherapy (ALLELE)

Abstract

Abstract Background: Epstein–Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) is an ultra-rare complication with low survival if initial treatment fails. Tabelecleucel is an off-the-shelf allogenic EBV-specific cytotoxic T cell therapy. Results from the overall population have been presented previously (Ghobadi et al. ASH 2024). Here we report for the first time, results from 12 pediatric patients who have participated in the ALLELE trial. Methods: ALLELE is a multicenter, open-label phase 3 trial. Eligibility criteria allow patients of any age to be included. During the trial, patients received intravenous tabelecleucel at 2 x 106 cells/kg on days 1, 8, and 15 in 35-day cycles. Response to treatment was evaluated by independent oncologic response adjudication (IORA) based on clinical and radiographic evidence collected during each treatment cycle. After treatment, disease status was evaluated for up to 2 years and survival status up to 5 years. The primary objective of the trial was objective response rate (ORR). Secondary objectives included rates of complete response (CR) and partial response (PR), time to response (TTR), duration of response (DOR), and overall survival (OS). Safety analyses were conducted in all patients who received at least one dose of tabelecleucel. Results: At data cutoff on 10 September 2024, a total of 86 patients (29 HCT and 57 SOT) ranging in age from 2.7–81.5 years were enrolled and treated with tabelecleucel. Of these patients, 12 were <17 years of age at the time of informed consent (3 HCT and 9 SOT). The median (range) age of pediatric patients was 8.8 (2.7–16.8) years. By age group, 2 patients were aged 2–<6 years, 5 were 6–<12 years and 5 were 12–<17 years. At the time of initial PTLD diagnosis, there were 9 pediatric patients with stage III (n=4) or stage IV (n=5) disease (Lugano classification with LYRIC modification), and 3 patients with the stage unknown. All 12 patients had extranodal disease and 8 had lymph node disease at screening. The median (range) time from PTLD diagnosis to receiving the first tabelecleucel dose was 2.99 (0.6–43.8) months. The ORR in patients <17 years of age was 50.0% (6/12 patients): CR was reported in 4/12 patients (1 HCT and 3 SOT), and PR was observed in 2/12 patients (1 HCT and 1 SOT). These results are consistent with the ORR for the overall population of 47.7% (41/86 patients). For the 6 patients who responded to treatment, the median (range) TTR was 1.6 (0.9–4.7) months. Two of the responders had a durable response of more than 6 months. Three of the responders, at the time of data cutoff, were censored with no disease progression or death. After a median (range) follow-up time of 5.2 (1.1–52.7) months, at time of data cutoff 50% (6/12 patients) were still alive, including 5 treatment responders and 1 non-responder. Serious adverse events (SAEs) were reported in 6 patients; in 2 cases they were deemed related to study treatment. Fatal SAEs were reported in 2 patients, neither of which was related to treatment. There were no reports of tumor flare reactions, infusion reactions, cytokine release syndrome, immune effector cell associated neurotoxicity, transmission of infectious diseases, graft vs host disease, or transplant rejection. Tabelecleucel showed a favorable safety profile consistent with that reported in the overall population. Conclusion: This analysis of 12 pediatric patients from the ALLELE trial suggests that the risk/benefit profile in the pediatric subgroup is consistent with that reported in the overall population, with an ORR of 50% (6/12 patients) and 5/6 treatment responders still alive at data cutoff. These findings support the use of tabelecleucel in pediatric patients with R/R EBV+ PTLD who have historically poor survival and very limited treatment options. The safety profile of tabelecleucel was favorable and no new concerns were identified for the pediatric population.