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Tabelecleucel (Ebvallo) monotherapy had a favorable risk-benefit profile in patients with Epstein-Barr virus (EBV)–positive post-transplant lymphoproliferative disease (PTLD) who were refractory to or had relapsed following treatment with rituximab (Rituxan) with or without chemotherapy after hematopoietic stem cell transplantation (HSCT) or solid organ transplant (SOT), according to updated data from a larger cohort of the phase 3 ALLELE trial (NCT03394365).1
Findings presented at the 51st Annual EBMT Meeting showed that the overall response rate (ORR) with tabelecleucel among all patients (n = 75) was 50.7% (95% CI, 38.9%-62.4%), comprising a complete response (CR) rate of 28.0% and a partial response rate (PR) rate of 22.7%. For patients who had undergone HCT (n = 26), the ORR was 50.0%, including a CR rate of 30.8% and PR rate of 19.2%. These respective rates for patients who had undergone solid organ transplant (n = 49) were 51.0%, 24.5%, and 26.5%.
The estimated median duration of response (DOR) for all responders (n = 38) was 23.0 months (95% CI, 12.1-not evaluable [NE]). For responders who had undergone HCT (n = 13) and solid organ transplant (n = 25), the respective DORs were 19.0 months (95% CI, 1.5-NE) and NE (95% CI, 6.8-NE). In the overall patient population, the median time to response (TTR) was 1.1 months (95% CI, 0.6-9.0), and the median time to best response was 1.6 months (95% CI, 0.6-9.0). In the HCT and solid organ transplant groups, the median TTRs were 1.0 month (95% CI, 0.6-9.0) and 2.0 months (95% CI, 0.7-4.7), respectively. The respective times to best response in these groups were 1.0 month (95% CI, 0.6-9.0) and 2.1 months (95% CI, 0.7-7.3).
The 12-month OS rate among all patients was 55.7%. Notably, the 12-month OS rate was superior in responders vs nonresponders, at 78.7% vs 28.2%, respectively. The median OS in the overall patient population, responders, and nonresponders was 18.4 months (95% CI, 5.7-NE), NE (95% CI, 18.6 months-NE), and 3.7 months (95% CI, 1.8-11.0), respectively. The 12-month progression-free survival (PFS) rate among responders was 71.9%, and the median PFS was 23.9 months.
“Tabelecleucel represents a transformative treatment for patients with relapsed/refractory EBV-positive PTLD,” presenting author Sridhar Chaganti, MD, PhD, MRCP, FRCPath, of the Centre for Clinical Haematology at the University Hospitals Birmingham NHS Foundation Trust, and coauthors wrote in a presentation of the data. “[This agent] had a promising ORR and OS in this difficult-to-treat patient population.”
Study Overview
ALLELE was a global, multicenter, open-label study evaluating tabelecleucel—an allogeneic, non-genetically modified, EBV-specific T-cell immunotherapy designed to target and eliminate cells infected with EBV in an HLA-restricted manner. The study enrolled patients with biopsy-proven EBV-positive PTLD who were relapsed/refractory to rituximab after prior allogeneic HCT or rituximab with or without chemotherapy following solid organ transplant who had an ECOG performance status (PS) of 3 or lower.
Intravenous tabelecleucel was administered at a dose of 2.0 x 106 cells/kg on days 1, 8, and 15 of each approximately 5-week treatment cycle. Patients underwent clinical and radiographic assessment on approximately day 28. Notably, patients received additional cycles of tabelecleucel until they achieved best response. Those who did not respond to the agent were permitted to switch to tabelecleucel using a T-cell line with different HLA restrictions. After the end of treatment, patients underwent disease assessment every 3 months for no more than 24 months, and survival status was evaluated every 6 months for no more than 5 years.
The study’s primary end point was ORR; key secondary end points included TTR, time to best response, OS in responders vs nonresponders, PFS in responders, and the rates of allograft loss/rejection episodes in the solid organ transplant subgroup.
Previously reported data from ALLELE showed that at a median follow-up of 14.1 months (IQR, 5.7-23.9), the ORR with tabelecleucel among patients who had received HCT (n = 14) was 50% (95% CI, 23%-77%). At a median follow-up of 6.0 months (IQR, 1.8-18.4), the ORR for patients who had received solid organ transplant (n = 29) was 52% (95% CI, 33%-71%).2
These data supported the FDA’s July 2024 decision to grant priority review to the biologics license application (BLA) seeking the approval of tabelecleucel monotherapy for this patient population.3 A complete response letter was subsequently issued for this application in January 2025.4
Baseline Characteristics
The median age of all patients was 44.4 years (range, 2.7-81.5), and the median ECOG performance status was 1 (range, 0-3); 26.5% of patients had an ECOG performance status of 2 or higher.1 Most patients were male (58.7%) and had extranodal disease at the time of screening (74.7%). Of the 68 PLTD-adapted prognostic index–evaluable patients, most had intermediate-risk PLTD (50.0%), followed by high-risk (42.6%) and low-risk (5.9%) disease. PLTD-adapted prognostic index information was unknown for 1 patient. Regarding PTLD morphology in the overall patient population, patients had diffuse large B-cell lymphoma (69.3%), plasmablastic lymphoma (4.0%), and other morphology (25.3%). The median times from transplant to EBV-positive PTLD diagnosis were 3.9 months (range, 0.6-66.0) and 10.8 months (range, 2.4-314.4) for patients who underwent HCT and solid organ transplant, respectively. The overall time from PTLD diagnosis to tabelecleucel treatment administration was 4.6 months (range, 0.6-190.5).
Patients had received a median of 1 (range, 1-5) prior line of systemic therapy, including rituximab monotherapy (86.7%), chemotherapy (46.7%), rituximab plus chemotherapy (37.3%), and immunotherapy (4.0%). For those who underwent standard organ transplant, transplant types included kidney (28.6%), heart (24.5%), lung (18.4%), liver (8.2%), and multivisceral (20.4%).
Tabelecleucel Exposure and Safety Data
Among all patients, the median number of tabelecleucel cycles was 2 (range, 1-6), and the median number of infusions was 6 (range, 1-18). The median duration of treatment was 1.9 months (range, 0.03-6.5). The number of inpatient infusions was 175, and 353 infusions were administered in the outpatient setting. Most patients (65.3%) received 1 line of tabelecleucel, followed by 2 lines (30.7%) and 3 lines (4.0%).
Regarding safety, treatment-emergent serious adverse effects (AEs) were experienced by 62.7% of patients, 8.0% of which were treatment related. Most treatment-emergent serious AEs and all fatal treatment-emergent serious AEs were not deemed treatment related.
No patients reported experiencing tumor flare reactions, infusion-related reactions, cytokine release syndrome, bone marrow rejection, immune effector cell–associated neurotoxicity syndrome, immunogenicity, or transmission of infectious diseases, including cytomegalovirus.
Graft-vs-host disease occurred in 11.5% of patients in the HCT arm, and bone marrow/organ rejection was reported by 6.1% of patients in the solid organ transplant arm; none of these cases were tabelecleucel related.
Disclosures: Chiganti reported receiving honoraria for service on advisory boards/consultancy for AbbVie, Kite/Gilead, Roche, Pierre Fabre, BMS-Celgene, Amgen, Sobi, and Autolus; receiving speaker fees from Takeda, Kite/Gilead, Incyte, AbbVie, Pierre Fabre, and Roche; and providing meeting attendance support for Takeda, Kite/Gilead, and Pierre Fabre.
References
Dierick D, Ghobadi A, Baiocchi R, et al. Updated results: multicenter open-label ph 3 study of tabelecleucel for SOT or HCT recipients with EBV+ PTLD after failure of rituximab or rituximab + chemotherapy. Presented at: EBMT 51st Annual Meeting; March 30-April 2, 2025. Florence, Italy. Abstract OS17-03.
Mahadeo KM, Baiocchi R, Beitinjaneh A, et al. Tabelecleucel for allogeneic haematopoietic stem-cell or solid organ transplant recipients with Epstein-Barr virus-positive post-transplant lymphoproliferative disease after failure of rituximab or rituximab and chemotherapy (ALLELE): a phase 3, multicentre, open-label trial. Lancet Oncol. 2024;25(3):376-387. doi:10.1016/S1470-2045(23)00649-6
Atara Biotherapeutics announces US FDA acceptance and priority review of the biologics license application for tabelecleucel (tab-cel) for the treatment of Epstein-Barr virus positive post-transplant lymphoproliferative disease. News release. Atara Biotherapeutics, Inc. July 17, 2024. Accessed April 2, 2025. https://investors.atarabio.com/news-events/press-releases/detail/356/atara-biotherapeutics-announces-u-s-fda-acceptance-and
Atara Biotherapeutics provides regulatory and business update on EBVALLO (tabelecleucel). News release. Atara Biotherapeutics. January 16, 2025. Accessed April 2, 2025. https://investors.atarabio.com/news-events/press-releases/detail/367/atara-biotherapeutics-provides-regulatory-and-business