Phase 2 EndRAD Study Shows Non-TBI Conditioning Maintains Efficacy in Pediatric B-ALL Transplant
核心洞察
The phase 2 EndRAD study demonstrated that removing total body irradiation from conditioning regimens achieved comparable efficacy outcomes in pediatric and young adult B-cell acute lymphoblastic leukemia (搜索) patients.
The study met its primary endpoint with 76.3% two-year event-free survival and 82% overall survival rates in NGS-MRD-negative patients receiving non-TBI conditioning.
Results from 51 treatment arm patients across 45 North American centers suggest non-TBI approaches may be considered for bone marrow NGS-MRD-negative patients.
The phase 2 EndRAD study has demonstrated that eliminating total body irradiation (TBI) from conditioning regimens does not compromise treatment efficacy in pediatric and young adult patients with B-cell acute lymphoblastic leukemia (搜索) (ALL). Results presented at the 2025 American Society of Hematology (搜索) Annual Meeting and Exposition showed that non-TBI conditioning achieved survival outcomes comparable to published TBI-based approaches.
Study Design and Patient Population
The multicenter trial enrolled 202 patients across 45 centers in North America between 2018 and 2025. The treatment arm included 51 patients designed to estimate survival after non-TBI myeloablative conditioning prior to allogeneic hematopoietic cell transplant (HCT) for next-generation sequencing minimal residual disease (NGS-MRD)-negative B-ALL (搜索). An additional 151 patients were enrolled in an observational arm receiving myeloablative HCT but were not eligible for the treatment arm.
Patients in the treatment arm were eligible if they were between 1 and 31 years old with high-risk complete remission 1 (CR1) or CR2 status. The median age was 13.5 years, with 51% being male. Receipt of prior CAR T-cell therapy and blinatumomab (Blincyto) was permitted. At the time of HCT, 49% of patients had CR1 and 51% had CR2.
Treatment Regimens and Donor Sources
The majority of treatment arm patients (86%) received busulfan, fludarabine, and thiotepa conditioning. Alternative regimens included fludarabine, melphalan, and thiotepa (6%), and fludarabine, melphalan, clofarabine, and thiotepa (6%).
Donor sources varied significantly: 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 grafts were used in 71% of patients, peripheral blood stem cell grafts in 21%, and unrelated cord blood grafts in 8%.
Primary Efficacy Outcomes
The study met its primary endpoint of event-free survival (EFS). The 2-year 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 aligned with the investigators' hypothesis that 2-year EFS and OS rates in NGS-MRD-negative patients receiving non-TBI regimens would be approximately 75% and 80%, respectively.
"OS and EFS in our phase 2 non-TBI treatment arm for NGS MRD-negative B-ALL (搜索) matched our hypothesis and were comparable with outcomes of patients who are MRD-negative receiving TBI in previous studies," concluded Dr. Hisham Abdel-Azim, chief of Transplant and Cellular Therapy at Loma Linda University Health (搜索).
Clinical Implications
The findings suggest that non-TBI conditioning approaches may offer a viable alternative for specific patient populations. "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. Abdel-Azim stated during the presentation.
The study excluded certain high-risk populations from the treatment arm, including infants under 1 year old, CR2 patients with a history of central nervous system relapse, those with T-cell ALL (搜索) and mixed-phenotype acute leukemia (搜索), and patients with active CNS/extramedullary disease at HCT. These patients were eligible for enrollment in the observational arm.