Two international clinical trials have shown for the first time that the bispecific T-cell engager blinatumomab, used in combination with conventional chemotherapy, offers a clear benefit to children with high-risk relapsed B-cell acute lymphoblastic leukemia (ALL). Both trials showed an advantage in overall survival (OS) for patients treated with blinatumomab, although only one also demonstrated a statistically significant difference in event-free survival (EFS). Results of the two trials were published in the Journal of the American Medical Association on March 2.
The first trial, led by Patrick A. Brown, MD, of Johns Hopkins University School of Medicine, enrolled 214 patients aged from 1 to 30 years in the United States, Canada, and Germany. At a median follow-up of 2.9 years, 2-year OS was 71.3% for blinatumomab-treated patients, compared with 58.4% for patients who received chemotherapy alone. Two-year disease-free survival (DFS) was 54.4% for the blinatumomab group versus 39.0% for the chemotherapy group. The trial was terminated early due to loss of clinical equipoise as a result of higher OS, DFS, and rates of MRD negativity, as well as lower rates of serious adverse events, in the blinatumomab group.
The second trial, led by Franco Locatelli, MD, PhD, of Sapienza University in Rome, Italy, enrolled 108 patients aged under 18 years in 13 countries. This trial was also terminated early, after a median follow-up of 22.4 months, when the pre-specified criterion for declaring blinatumomab superiority was met. The 2-year estimate of the EFS rate was 66.2% for the blinatumomab group, compared with 27.1% for the chemotherapy group. The hazard ratio for OS was 0.43. Ninety percent of patients in the blinatumomab group achieved MRD-negative remission, compared with 54% in the chemotherapy group; 88.9% of those in the blinatumomab group, versus 70.4% in the chemotherapy group, proceeded to allogeneic stem cell transplant. In both trials, patients treated with blinatumomab experienced lower rates of serious adverse events.
These results “support investigating the inclusion of blinatumomab and other immunotherapies in future clinical trials of frontline treatment and therapy for relapse among patients with childhood ALL,” wrote Neerav Shukla, MD, and Maria Luisa Sulis, MD, of Memorial Sloan Kettering Cancer Center, in an accompanying editorial.
– Brown PA, Ji L, Xu X, et al. Effect of Postreinduction Therapy Consolidation With Blinatumomab vs Chemotherapy on Disease-Free Survival in Children, Adolescents, and Young Adults With First Relapse of B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA. 2021;325(9):833-842. doi:10.1001/jama.2021.0669
– Locatelli F, Zugmaier G, Rizzari C, et al. Effect of Blinatumomab vs Chemotherapy on Event-Free Survival Among Children With High-risk First-Relapse B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA. 2021;325(9):843-854. doi:10.1001/jama.2021.0987
– Shukla N, Sulis ML. Blinatumomab for Treatment of Children With High-risk Relapsed B-Cell Acute Lymphoblastic Leukemia. JAMA. 2021 Mar 2;325(9):830-832. doi: 10.1001/jama.2021.1395