FDA Accepts BLA Resubmission for Tabelecleucel in EBV+ Post-Transplant Lymphoproliferative Disease

The FDA has accepted the resubmitted biologics license application (BLA) seeking the approval of tabelecleucel (Ebvallo), an allogeneic, off-the-shelf, Epstein-Barr virus (EBV)–specific T-cell immunotherapy, as monotherapy for the treatment of adult and pediatric patients 2 years of age and older with EBV-positive post-transplant lymphoproliferative disease (PTLD) who have received at least 1 prior therapy.¹

Under the Prescription Drug User Fee Act, the agency set a target action date of March 31, 2027.

The resubmission, which represents the third BLA submission for the agent, was based on alignment reached with the FDA at a Type A meeting in April 2026.^1,2 It includes an updated dataset with additional patients and longer follow-up from the ongoing, pivotal, single-arm phase 3 ALLELE trial (NCT03394365), as well as supplemental data from expanded access programs, a separate clinical study, and commercial experience in Europe.¹

In an updated analysis of ALLELE presented at the 2024 ASH Annual Meeting and Exposition, tabelecleucel (n = 75) produced an objective response rate (ORR) of 50.7% (95% CI, 38.9%-62.4%), including a complete response rate of 28.0%.³ The median duration of response was 23.0 months (95% CI, 12.1-not estimable [NE]), and the median overall survival (OS) was 18.4 months (95% CI, 6.9-NE). The ORR was 50.0% among patients who had undergone allogeneic hematopoietic cell transplant (HCT; n = 26) and 51.0% among those who had undergone solid organ transplant (SOT; n = 49).

“[If approved,] I think this will be an important treatment for patients with refractory PTLD. [Considering] the fact that there is no standard approach right now, choosing an approach that has meaningful benefit with this really [safety] favorable profile will be really important for patients,” Kris M. Mahadeo, MD, MPH, said in an interview with OncLive® earlier in 2026. Mahadeo is division chief and professor of pediatrics at Duke University School of Medicine in Durham, North Carolina.

What is the mechanism of action of tabelecleucel?

Tabelecleucel is an allogeneic, off-the-shelf T-cell immunotherapy designed to target and eliminate EBV-infected cells.¹ The product is not genetically modified and recognizes EBV-infected cells in an HLA-restricted manner.²

The agent received marketing authorization in the European Union in December 2022, in the United Kingdom in May 2023, and in Switzerland in May 2024.¹ In the United States, tabelecleucel remains investigational and is available through clinical trials and expanded access. According to Pierre Fabre, the median survival for patients with EBV-positive PTLD whose initial therapy fails is 3 weeks following HCT and 4.1 months following SOT.¹

Why did the FDA issue prior complete response letters?

The FDA originally accepted the tabelecleucel BLA, then held by Atara Biotherapeutics, in July 2024 and granted it priority review, with a target action date of January 15, 2025.² In January 2025, the agency issued a complete response letter (CRL) tied solely to findings from an inspection of a third-party manufacturing facility; no clinical efficacy or safety deficiencies were identified.

The resubmitted BLA was accepted with priority review in July 2025, supported by data from more than 430 patients. In January 2026, the FDA issued a second CRL. Although the agency acknowledged that the manufacturing issue had been resolved and raised no safety concerns, it stated that it no longer considered the single-arm ALLELE study sufficient to support accelerated approval and requested a new study.

At the subsequent Type A meeting, the FDA agreed that a single-arm study with an appropriate, prespecified historical control that is applicable to the trial population could represent an adequate and well-controlled study, setting the stage for the current resubmission.

How was the ALLELE trial designed?

The open-label, multicenter phase 3 ALLELE trial enrolled patients of any age with biopsy-proven EBV-positive PTLD.^2,3 Patients who had undergone allogeneic HCT were required to have disease that relapsed after or was refractory to rituximab (Rituxan) or a rituximab biosimilar, and patients who had undergone SOT were required to have disease that relapsed after or was refractory to rituximab with or without chemotherapy.

Patients were enrolled into 3 cohorts: SOT recipients whose disease progressed on rituximab alone, SOT recipients whose disease progressed on rituximab plus chemotherapy, and HCT recipients whose disease progressed on rituximab. An ECOG performance status of 3 or lower was required.

Patients received intravenous tabelecleucel at 2 × 10⁶ cells/kg on days 1, 8, and 15 of each 35-day cycle. ORR was the primary end point. The median time to response in the updated analysis was 1.1 months (range, 0.6-9.0), and the 12-month OS rate was 55.7%.

What is the safety profile of tabelecleucel?

In the updated analysis, serious treatment-emergent adverse effects (TEAEs) occurred in 62.7% of patients, including 65.4% of HCT recipients and 61.2% of SOT recipients; 8.0% of patients had serious TEAEs considered related to tabelecleucel.^3,4 Fatal TEAEs occurred in 19.2% of the HCT cohort and 18.4% of the SOT cohort, none of which were considered related to treatment.

No cases of tumor flare, infusion reactions, cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, or transmission of infectious disease were reported, and no graft-vs-host disease or organ rejection was attributed to tabelecleucel.

References

1. Pierre Fabre Pharmaceuticals announces FDA acceptance of BLA resubmission for tabelecleucel for the treatment of Epstein-Barr virus-positive post-transplant lymphoproliferative disease. News release. Pierre Fabre Pharmaceuticals. October 14, 2026. Accessed October 14, 2026. https://www.prnewswire.com/news-releases/pierre-fabre-pharmaceuticals-announces-fda-acceptance-of-bla-resubmission-for-tabelecleucel-for-the-treatment-of-epstein-barr-virus-positive-post-transplant-lymphoproliferative-disease-302908451.html
2. Tabelecleucel BLA is resubmitted to FDA for EBV post-transplant lymphoproliferative disease. OncLive. Published September 30, 2026. Accessed October 14, 2026. https://www.onclive.com/view/tabelecleucel-bla-is-resubmitted-to-fda-for-ebv-post-transplant-lymphoproliferative-disease
3. Ghobadi A, et al. Updated clinical results: a multicenter, open-label, phase 3 study of tabelecleucel for Epstein-Barr virus-positive post transplant lymphoproliferative disease after failure of rituximab or rituximab plus chemotherapy. Blood. 2024;144(suppl 1):70. doi:10.1182/blood-2024-198159
4. Mahadeo KM, 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