Children, adolescents, and young adult patients in first B-cell acute lymphoblastic leukemia relapse did not experience a statistically significant disease-free survival benefit with blinatumomab treatment compared with chemotherapy.
There was no statistically significant difference in disease-free survival between postreinduction treatment with blinatumomab (Blincyto) and treatment with chemotherapy for children, adolescents, and young adult patients with first relapse of B-cell acute lymphoblastic leukemia (B-ALL) who went on to receive hematopoietic stem cell transplant, according to data published in JAMA.
Focusing on a median follow-up time of 2.9 years, the 2-year disease-free survival rate was 54.4% for patients in the blinatumomab group compared with 39.0% for patients in the chemotherapy group (HR, 0.70; 95% CI, 0.47-1.03; 1-sided P = .03). More, the 2-year overall survival rate was recorded at 71.3% for patients in the blinatumomab group and 58.4% for patients the chemotherapy group (HR, 0.62; 95% CI, 0.39-0.98; 1-sided P = .02).
The patient population from the phase 3 trial (NCT02101853) consisted of 208 patients with a median age of 9 years, 118 (57%) of whom completed the randomized therapy. The data and safety monitoring committee recommended a termination of the randomization, with 80 of 131 planned events occurring to that point.
Both treatment options were followed by transplant, but interpretation of the study results are limited due to the early termination with “possible underpowering for the primary end point.”
“Because the randomization was terminated early by the independent data and safety monitoring board, the primary analysis set included 208 patients instead of the planned 220, so it is possible that the trial was underpowered for the primary endpoint of disease-free survival,” wrote the investigators.
For the blinatumomab group, the safety profile featured serious adverse events such as infection (15%), febrile neutropenia (5%), sepsis (2%), and mucositis (1%). In the chemotherapy group, some serious adverse events included infection (65%), febrile neutropenia (58%), sepsis (27%), and mucositis (28%).
“The survival benefit of blinatumomab compared with chemotherapy is likely derived from the percentage of patients who were able to undergo transplant,” wrote the investigators. “This trial was designed for all patients to receive 2 cycles of either chemotherapy or blinatumomab followed by transplant.”
The trial was conducted by Children’s Oncology Group at 155 facilities across the United States, Canada, Australia, and New Zealand. Eligible patients ranged in ages from 1 to 30 years with B-ALL first relapse and were enrolled between December 2014 and September 2019.
The primary end point of the research was disease-free survival, with a key secondary end point of overall survival.
The main limitation of the data focuses on the early termination of high- and intermediate-risk randomization, suggesting the disease-free survival may be underpowered. More, the potential interpretation of secondary, exploratory, and post hoc end points is limited due to the “lack of planned adjustment for multiple comparisons.”
“Postreinduction treatment with blinatumomab compared with chemotherapy, followed by hematopoietic stem cell transplant, did not result in a statistically significant difference in disease-free survival, but study interpretation is limited by early termination with possible underpowering for the primary end point,” wrote the investigators.
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. JAMA. 2021;325(9):833-842. doi:10.1001/jama.2021.0669