Landmark Trial Suggests TBI-Free Conditioning is Viable Option for Young B-ALL Patients
ORLANDO, FL – New data presented this week suggest that pediatric and young adult patients with B-cell acute lymphoblastic leukemia (B-ALL) who achieve minimal residual disease (MRD) negativity via next-generation sequencing (NGS) may safely forgo total body irradiation (TBI) as part of their pre-transplant conditioning regimen.results from the phase 2 endrad trial (PTCTC ONC1701) demonstrate outcomes comparable to those achieved with TBI-based conditioning, potentially reducing the significant long-term side effects associated with TBI.
The study, conducted across 45 North American centers between 2018 and 2025, enrolled a total of 202 patients. Researchers evaluated survival rates following non-TBI myeloablative conditioning prior to allogeneic hematopoietic cell transplant (HCT) in 51 patients with NGS-MRD-negative B-ALL (the treatment arm). The remaining 151 patients, who were ineligible for the treatment arm, received standard myeloablative HCT and comprised the observational arm.
“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,” stated Dr. Hisham Abdel-Azim, chief of Transplant and cellular Therapy at Loma Linda University Health, during the presentation.
The most common conditioning regimen in the treatment arm was busulfan, fludarabine, and thiopeta (86%), with smaller proportions receiving choice combinations of fludarabine, melphalan, and thiopeta (6%), or fludarabine, melphalan, clofarabine, and thiopeta (6%).
Researchers hypothesized that 2-year event-free survival (EFS) and overall survival (OS) rates in NGS MRD-negative patients receiving a non-TBI regimen woudl be approximately 75% and 80%, respectively. Dr. Abdel-Azim confirmed that the study results aligned with these predictions and were comparable to outcomes seen in previous studies of MRD-negative patients receiving TBI.
eligibility for the treatment arm was limited to patients aged 1-31 years with high-risk complete remission 1 (CR1) or CR2 status.Prior CAR T-cell therapy and blinatumomab (Blincyto) were permitted. Exclusion criteria for the treatment arm included age under one year,CR2 status with a history of central nervous system relapse,T-cell ALL and mixed-phenotype acute leukemia,and active CNS/extramedullary disease at the time of HCT.
The median age of patients in the treatment arm was 13.5 years (range, 2.3-30.5), with 51% being male.Donor sources varied, with 37% receiving HLA-matched sibling donors, 35% mismatched/unrelated haploidentical donors, 20% matched unrelated donors, and 8% unrelated cord blood donors. Bone marrow was the graft source for 71% of patients,while 21% received peripheral blood stem cells and 8% received cord blood grafts.At the time of HCT, 49% of patients were in CR1 and 51% were in CR2.
This research offers a potentially significant advancement in the treatment of B-ALL, a cancer affecting approximately 2,500 children and young adults in the United States each year. TBI,while effective,is known to cause long-term complications including infertility,secondary cancers,and neurocognitive deficits. Identifying patients who can achieve durable remission with less toxic conditioning regimens represents a crucial step towards improving the quality of life for survivors.
“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.
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
Disclosure: Dr. Abdel-Azim has disclosed consultancy relationships with Kite, Novartis, Adaptive, Vertex, and Johnson and Johnson, as well as research funding
