Cell therapy a ‘meaningful’ advance for post-transplant lymphoproliferative disease
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More than half of patients treated with tabelecleucel for Epstein-Barr virus-driven post-transplant lymphoproliferative disease responded to therapy, phase 3 study results showed.
Tabelecleucel (Atara Biotherapeutics) is an allogeneic, nongene-edited, Epstein-Barr virus (EBV)-specific T-cell therapy.
The agent is derived from previously untreated peripheral blood mononuclear cells from unrelated donors that are separated, cultured and expanded to produce an IV infusion of T cells that specifically target EBV-infected cells.
A planned interim analysis of the ALLELE trial — presented at Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR — suggest a clinically meaningful increase in OS among patients who respond to the investigational cell therapy, according to researchers.
Background
EBV-driven post-transplant lymphoproliferative disease (PTLD) is a potentially life-threatening complication that arises from allogeneic hematopoietic stem cell or solid organ transplantation.
There are no FDA-approved treatments, according to Susan E. Prockop, MD, program director for clinical and translational research and member of the pediatric stem cell transplant team at Boston Children’s Hospital.
PTLD typically is treated with a combination of rituximab (Rituxan, Genentech), chemotherapy and radiation, depending on the primary cause of the disease.
Prockop said research presented at last year’s ASH Annual Meeting and Exposition showed poor median OS for patients with EBV-driven PTLD that progresses after first-line therapy, ranging from 0.7 months for HSCT recipients to 4.1 months for those who received a solid organ transplant.
“Patients who do not respond to initial therapy have few treatment options,” Prockop said during a presentation. “Alternative therapies are needed for both of these patient cohorts.”
Methods
The planned interim analysis of the multicenter ALLELE trial included 38 patients (median age, 52.9 years; range, 3.2-81.5; 55.3% male) with EBV-driven PTLD who experienced disease progression after first-line therapy with rituximab for HSCT recipients (n = 14) or rituximab plus chemotherapy for patients who received solid organ transplant (n = 24).
Study participants received infusions of tabelecleucel at a dose of 2 × 106 cells/kg on days 1, 8 and 15 of a 35-day treatment cycle. Tabelecleucel is produced for a variety of HLA profiles and matched to the recipient based on HLA restrictions and allele profiles.
Patients received additional treatment cycles until they met end-of-treatment criteria or experienced unacceptable toxicity.
All 38 patients treated with tabelecleucel had a 6-month follow-up evaluation as of the data cutoff date of May 7, 2021. Median follow-up was 9.4 months (range, 0.4-32.1).
Key findings
Results showed an overall response rate of 50% (95% CI, 33.4-66.6) for the entire study population.
Half of patients in both the solid organ transplant (95% CI, 29.1-70.9) and HSCT (95% CI, 23-77) groups responded to therapy.
Investigators noted a 26% complete response rate for the overall study population, with 36% in the HSCT group and 21% in the solid organ transplant group achieving complete response.
Median time to response in the entire study population was 1.1 month (range, 0.7-4.7).
Eleven (57.8%) of the 19 patients who responded to treatment had response that lasted at least 6 months. Median duration of response had not been reached.
Researchers reported median OS of 18.4 months (range, 6.9 to not reached) for all patients and 16.4 months (range, 3.5 to not reached) for solid organ transplant recipients. Median OS had not been reached for those who underwent HSCT.
Further analysis showed estimated 1-year OS of 61.1% for all study participants. Patients who responded to therapy with tabelecleucel had a noticeably higher estimated 1-year OS rate compared with nonresponders (89.2% vs. 32.4%).
Most patients (60.5%) experienced grade 3 or greater treatment-emergent adverse events. Researchers reported no cases of graft-versus-host disease, infusion-related reaction, tumor flare, cytokine release syndrome, organ rejection or bone marrow rejection related to the use of tabelecleucel.
Clinical implications
Tabelecleucel has shown meaningful clinical benefit in previous single-center and multicenter studies, with similar response rates and OS when compared with interim analysis of the ALLELE trial, Prockop said.
“Tabelecleucel was well-tolerated, without evidence of the toxicities frequently seen in the context of chimeric antigen receptor and other T-cell modalities,” she said. “These results ... represent a potential meaningful treatment advance for these patients with high unmet need for whom there are no approved therapies.”
References:
Dharnidharka V, et al. Abstract 2528. Presented at: ASH Annual Meeting and Exposition; Dec. 11-14, 2021; Atlanta.
Prockop SE, et al. Abstract 23. Presented at: Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; April 23-26, 2022; Salt Lake City.
Sanz J, et al. Abstract 1454. Presented at: ASH Annual Meeting and Exposition; Dec. 11-14, 2021; Atlanta.
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