Among pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL), the removal of total body irradiation (TBI) from conditioning did not compromise efficacy, and was comparable to published outcomes, study results have shown.
Findings from the phase 2 EndRAD study were presented at the 2025 American Society of Hematology Annual Meeting and Exposition.
The two-year event-free survival (EFS) rate in the treatment arm was 76.3%, and the two-year overall survival (OS) rate was 82%. These results showed that the primary end point of the trial of EFS was met.
Glossary
Event-free survival (EFS): the length of time after treatment during which a patient has no major setbacks, such as the cancer coming back, getting worse, or serious side effects that stop treatment.
Overall survival (OS): the total length of time from diagnosis or the start of treatment that a patient is still alive, regardless of whether the cancer has returned or progressed.
Minimal residual disease (MRD): a very small number of cancer cells that remain in the body after treatment, often too few to be seen with standard tests.
Allogeneic hematopoietic cell transplant: a procedure in which a patient receives blood-forming stem cells from a donor — usually a relative or a matched volunteer.
“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,” Dr. Hisham Abdel-Azim, 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 (51 patients) 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 (151 patients), patients were given myeloablative HCT and were not eligible for the treatment arm.
Abdel-Azim stated he and his colleagues hypothesized that the two-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 Blincyto (blinatumomab) 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, 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.
Reference
- “ 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” by Dr. Hisham Abdel-Azim, et al., Blood.
For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.
