In the phase III ALLELE trial reported in The Lancet Oncology, Mahadeo et al found that the Epstein-Barr virus (EBV)-specific T-cell immunotherapy tabelecleucel produced high response rates—and few of the toxicities associated with other adoptive T-cell therapies—in allogeneic hematopoietic stem cell transplant (HSCT) or solid organ transplant recipients with EBV-positive posttransplantation lymphoproliferative disease after failure of rituximab or rituximab and chemotherapy.

As stated by the investigators, “With recent [European Union] marketing authorization, tabelecleucel is the first off-the-shelf, allogeneic, EBV-specific T-cell immunotherapy to receive approval for treatment of relapsed or refractory EBV-positive [posttransplant] lymphoproliferative disease.”

Study Details

In the international trial, 63 patients aged 22 to 65 years, including 14 who had undergone allogeneic HSCT and 29 who were solid organ transplant recipients, were enrolled between June 2018 and November 2021. Patients received tabelecleucel at 2 × 10⁶ cells/ kg on days 1, 8, and 15 in 35-day cycles. The primary endpoint was objective response rate.

Responses

Objective response was observed in 7 (50%, 95% confidence interval [CI] = 23%–77%) of 14 patients in the HSCT group, including complete response in 6 (43%), and in 15 (52%, 95% CI = 33%–71%) of 32 in the solid organ transplant group, including complete response in 6 (21%). In the combined groups, objective response was observed in 22 (51%, 95% CI = 36%–67%). Median duration of response was 23.0 months (95% CI = 15.9 months to not estimable) among responders in the HSCT group and 15.2 months (95% CI = 1.2 months to not estimable) among responders in the solid organ transplant group.

Estimated 1-year overall survival for responders vs nonresponders was 100% vs 35.7% (P = .014) in the HSCT group, 75.2% vs 33.6% (P = .016) in the solid organ transplant group, and 84.4% vs 34.8% (P = .0009) in the total population.

Adverse Events

The most common adverse events of any grade were pyrexia (36% of HSCT group, 28% of solid organ transplant group) and diarrhea (29% and 28%); the most common grade ≥ 3 adverse event was decreased neutrophil count (29% and 14%). Serious adverse events occurred in 53% of patients overall.

Grade ≥ 3 treatment-related serious adverse events were reported in two patients, consisting of grade 4 erythematous rash and grade 3 hypotension in one patient and grade 3 hypoxia in the other. Fatal adverse events—none considered related to treatment—occurred in five patients (12%).

There were no reports of tumor flare reaction, cytokine-release syndrome, immune effector cell–associated neurotoxicity syndrome, transmission of infectious diseases, marrow rejection, or infusion reactions. No treatment-related graft-vs-host disease or solid organ transplant rejection was observed.

The investigators concluded, “Tabelecleucel provides clinical benefit in patients with relapsed or refractory EBV-positive [posttransplant] lymphoproliferative disease, for whom there are no other approved therapies, without evidence of safety concerns seen with other adoptive T-cell therapies. These data represent a potentially transformative and accessible treatment advance for patients with relapsed or refractory disease with few treatment options.”

Susan Prockop, MD, of the Department of Pediatrics, Boston Children's Hospital–Dana Farber Cancer Institute, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Atara Biotherapeutics. For full disclosures of the study authors, visit thelancet.com.