Tabelecleucel Shows Sustained Efficacy in EBV+ PTLD, FDA Decision Expected in January 2025
Key Insights
Tabelecleucel demonstrates a 50.7% objective response rate in patients with relapsed or refractory EBV+ PTLD (search) after transplant, according to Phase 3 ALLELE study results.
The median duration of response to tabelecleucel was 23 months, with a median overall survival of 18.4 months, indicating a durable treatment effect.
Safety findings were consistent with prior studies, showing no new safety signals like cytokine release syndrome or immune effector cell-associated neurotoxicity.
Updated results from the Phase 3 ALLELE study, presented at the 66th American Society of Hematology (ASH) Annual Meeting, confirm the efficacy and safety of tabelecleucel in patients with relapsed or refractory Epstein-Barr virus-positive post-transplant lymphoproliferative disease (search) (EBV+ PTLD (search)). The study, involving adults and children aged two years and older, evaluated tabelecleucel following solid organ transplant (SOT) or hematopoietic cell transplant (HCT) after failure of rituximab or rituximab plus chemotherapy.
The ALLELE study's data encompassed a larger cohort of 75 patients (49 SOT, 26 HCT) compared to previously published data. Patients treated with tabelecleucel achieved a 50.7% objective response rate (ORR), with SOT ORR at 51.0% and HCT ORR at 50.0%. The median duration of response was 23 months, and the median overall survival was 18.4 months.
Clinician Perspective
"These clinically meaningful results highlight the potential of tabelecleucel in improving survival for R/R EBV+ PTLD (search) patients, who after undergoing a potentially life-saving solid organ or hematopoietic cell transplant suddenly face yet another life-threatening illness. Currently, these patients have no FDA-approved treatment options and experience poor overall survival of only weeks to a few months following the failure of first-line treatment," said Armin Ghobadi, MD, Professor of Medicine and Clinical Director of the Center for Gene and Cellular Immunotherapy at Washington University in St. Louis.
Study Design and Treatment Regimen
Patients received a median of two cycles of tabelecleucel therapy. Each cycle included three infusions given on days 1, 8, and 15, with efficacy assessed around day 28. Infusions were administered on an outpatient basis 67% of the time.
Safety Profile
Safety findings were consistent with previously published data. Serious treatment-emergent adverse events (TEAEs) were reported in 65.4% and 19.2% of HCT patients and 61.2% and 18.4% of SOT patients, respectively. No fatal TEAEs were reported as treatment-related, and there were no reports of cytokine release syndrome, tumor flare, infusion reactions, immune effector cell-associated neurotoxicity syndrome, or transmission of infectious diseases. No events of graft vs host disease or organ rejection were reported as tabelecleucel related.
Regulatory Status and Future Implications
The FDA accepted the Biologics License Application (BLA) for tabelecleucel in August 2024, granting priority review for its use as monotherapy in adult and pediatric patients two years of age and older with EBV+ PTLD (search) who have received at least one prior therapy. The Prescription Drug User Fee Act (PDUFA) target action date is January 15, 2025.
If approved, tabelecleucel would be the first approved allogeneic, off-the-shelf, T-cell therapy in the U.S. and the only FDA-approved treatment for R/R EBV+ PTLD (search), an ultra-rare, acute, and potentially deadly hematologic malignancy that occurs after life-saving transplantation.
About Tabelecleucel
Tabelecleucel is an allogeneic, off-the-shelf, EBV-specific T-cell immunotherapy designed to selectively target and eliminate EBV-infected cells. Unlike autologous CAR-T therapies, allogeneic T-cells are derived from third-party donors and are not genetically modified. Immune cells are collected from the blood of healthy donors and exposed to Epstein-Barr virus (search) antigens to help enrich for T cells that recognize EBV. These EBV T cells are expanded, characterized, kept alive, and stored for future use to treat patients.
Tabelecleucel was granted marketing authorization under the brand name EBVALLO® in December 2022 by the European Commission (EC) as a monotherapy for the treatment of adult and pediatric patients two years of age and older with r/r EBV+ PTLD (search) who have received at least one prior therapy.