Immunotherapy with blinatumomab improved disease-free survival for patients with first relapse of B-cell acute lymphoblastic leukemia (ALL), although the results were not statistically significant, according to a recent study published in the Journal of the American Medical Association. Randomization for the study was terminated early, which could have caused the data to be underpowered for the primary end point.
Children, adolescents, and young adults have poor survival with first relapse of B-cell ALL, particularly for early relapse. Additionally, standard chemotherapy has a high rate of toxicities for patients with first relapse ALL.
The study authors sought to determine whether blinatumomab could replace intensive chemotherapy in this patient population. The primary endpoint was disease-free survival with a threshold of statistical significance at a 1-sided P <.025.
Randomization was ended early after a planned interim analysis found 80 of 131 anticipated events occurred. The stopping rule was not met, but blinatumomab had higher rates of disease-free survival and overall survival, lower toxicity, and more minimal residual disease (MRD) clearance. The data and safety monitoring committee determined these factors demonstrated a loss of clinical equipoise.
A total of 214 patients aged 1 to 30 years old (median 9 years) with high- and intermediate-risk first relapse of B-cell ALL were randomly assigned 1:1 to each group. The 2-year disease-free survival was 54.4% for the group receiving blinatumomab and 39% for those receiving chemotherapy (P =.03). Blinatumomab had significantly improved overall survival than chemotherapy (71.3% vs 58.4%, P =.02).
The authors also set an exploratory endpoint of MRD clearance. After the first cycle of therapy, 75% of patients in the blinatumomab group had MRD negativity vs 32% for the chemotherapy group (P <.001).
The blinatumomab group had lower cumulative rates of adverse events – particularly for infection, febrile neutropenia, mucositis, and sepsis – than the chemotherapy group.
Overall, postreinduction therapy with blinatumomab followed by hematopoietic stem cell transplantation did not produce a statistically significant difference in disease-free survival compared to postreinduction therapy with chemotherapy followed by transplant. However, early termination of randomization may have caused the results to be underpowered.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
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