Efficacy Outcomes Remain Consistent Without Total Body Irradiation in B-ALL

The phase 2 EndRAD study (NCT03509961) found that removing total body irradiation (TBI) from conditioning did not compromise efficacy in pediatric or young adult patients with B-cell acute lymphoblastic leukemia (ALL) and was comparable to published outcomes. The results were presented at the 2025 American Society of Hematology Annual Meeting and Exposition.

The 2-year event-free survival (EFS) rate in the treatment arm was 76.3% (95% CI, 61.1%-86.1%), and the 2-year overall survival (OS) rate was 82.0% (95% CI, 67.1%-90.6%). These results showed that the primary end point of the trial of EFS was met.

“Based upon this data, pediatric and young adult patients who are bone marrow next-generation sequencing (NGS)-minimal residual disease (MRD)-negative may consider non-TBI approaches as they choose therapy,” Hisham Abdel-Azim, MD, chief of Transplant and Cellular Therapy at Loma Linda University Health, said during the presentation.

A total of 202 patients were enrolled in the trial. The treatment arm (n = 51) was designed to estimate survival after non-TBI myeloablative conditioning prior to allogeneic hematopoietic cell transplant (HCT) for NGS-MRD-negative B-ALL. A total of 86% of patients were given busulfan, fludarabine, and thiopeta. Other comparable therapies included fludarabine, melphalan, and thiopeta (6%), and fludarabine, melphalan, clofarabine, and thiopeta (6%). In the observational arm (n = 151), patients were given myeloablative HCT and were not eligible for the treatment arm.

Abdel-Azim stated he and his colleagues hypothesized that the 2-year EFS and OS rates in patients who are NGS MRD negative and receiving a non-TBI-based regimen would be around 75% and 80%, respectively. The study was conducted in 45 centers in North America between 2018 and 2025.

Infants were not allowed in the treatment arm, and young children who were not eligible and received non-TBI treatment were included in the observational arm. Additionally, the observational arm included those who were flow-negative but NGS-positive who received TBI.

In the treatment arm, patients were eligible for treatment if they were between 1 and 31 years old and had high-risk complete remission 1 (CR1) or CR2 status. Receipt of prior CAR T-cell therapy and blinatumomab (Blincyto) was allowed. Patients were excluded from the treatment arm but were eligible to enroll on the observational arm if they were less than 1 year old, CR2 with a history of central nervous system relapse, had T-cell ALL and mixed-phenotype acute leukemia, and had active CNS/extramedullary disease at HCT.

In the treatment arm, the median age was 13.5 years (range, 2.3-30.5), and 51% of patients were male. Additionally, 37% had HLA-matched sibling donors, 35% had mismatched/unrelated haploidentical donors, 20% had matched unrelated donors, and 8% had unrelated cord blood donors. Bone marrow graft was given in 71% of patients, peripheral blood stem cell graft was given to 21% of patients, and 8% received an unrelated cord blood graft. Additionally, at HCT, 49% of patients had CR1 and 51% had CR2.

“OS and EFS in our phase 2 non-TBI treatment arm for NGS MRD-negative B-ALL matched our hypothesis and were comparable with outcomes of patients who are MRD-negative receiving TBI in previous studies,” Abdel-Azim concluded.

Abdel-Azim disclosures: Kite, consultancy; Novartis, consultancy; Adaptive, consultancy and research funding; Vertex, consultancy; and Johnson and Johnson, consultancy.

Reference

Abdel-Azim H, Quigg T, Kapoor N, et al. High event-free (EFS) and overall survival (OS) after non-total body irradiation (TBI) conditioning and allogeneic hematopoietic cell transplantation (HCT) in next-generation-sequencing minimal residual disease (NGS-MRD) negative B-acute lymphoblastic leukemia (B-ALL): Results from the EndRAD trial (PTCTC ONC1701). Blood. 2025;146(suppl 1):163. doi:10.1182/blood-2025-163