In pediatric patients with newly diagnosed standard-risk B-cell acute lymphoblastic leukemia (B-ALL), adding Blincyto (blinatumomab) to chemotherapy significantly improved 3-year disease-free survival (DFS) rates compared with chemotherapy alone.
Patients eligible for the treatment combination are at average or high risk for relapse, according to findings from the interim analysis of the Children’s Oncology Group Study AALL1731, presented during a press briefing ahead of the 2024 ASH Annual Meeting.
At a median follow-up of 2.5 years, the three-year DFS rate in the overall population of 1,440 patients was 96% with Blincyto plus chemotherapy versus 87.9% with chemotherapy alone. In the standard risk-average population, these respective rates were 97.5% (417 patients) and 90.2% (418 patients). In the standard risk-high population, respective rates were 94.1% (301 patients) and 84.8% (304 patients).
Additionally, Blincyto plus chemotherapy reduced rates of bone marrow relapse versus chemotherapy alone in the overall population, as well as in the standard risk-average and standard risk-high populations. Patients who received Blincyto also had a numerically lower cumulative incidence of central nervous system (CNS) relapses versus those who received chemotherapy alone.
“The improvement in DFS was secondary to a significant reduction in bone marrow relapses,” lead study author Dr. Rachel E. Rau, stated in a presentation of the data. “We did not see similar reduction in the [rarer] event of an isolated CNS relapse. This finding was not surprising, given [Blincyto’s] known limited activity in the CNS.”
Rau is an associate professor of pediatrics at the University of Washington and a pediatric hematologist-oncologist at Seattle Children’s Hospital in Washington.
DFS and Safety of Blincyto Plus Chemotherapy in Pediatric B-ALL
A subset analysis in prognostically relevant patient subsets showed that the addition of Blincyto significantly improved DFS outcomes versus chemotherapy alone, regardless of patient sex, most races/ethnicities, cytogenetic risk and end-of-induction bone marrow minimal residual disease (MRD) levels.
“[These findings indicate] that, to an extent, Blincyto neutralizes many of the known or prognostic features of B-ALL,” Rau explained.
Regarding safety, Blincyto target toxicities reported in 624 patients in the first cycle of treatment included cytokine release syndrome (CRS), seizure and encephalopathy (brain disease that alters brain function). Blincyto target toxicities reported in 552 patients during the second cycle of treatment included CRS and seizure. No encephalopathy was reported during the second cycle of Blincyto.
In the standard risk-average population, higher rates of grade 3 (severe) or higher infectious toxicities were seen in the Blincyto group of 351 patients versus the chemotherapy alone group of 376 patients, including febrile neutropenia (low blood cell count and a fever), sepsis (body’s overreaction to an infection) and catheter-related infections (flexible tube inserted into bladder) and other infections.
“Most of the differences in the rates [of sepsis and catheter-related infections] were attributable to increased events in the chemotherapy blocks that followed [Blincyto] therapy,” Rau said.
In the standard risk–high population, higher rates of grade 3 or higher febrile neutropenia, sepsis and catheter-related infections were also seen in the Blincyto group versus the chemotherapy alone group. However, the rate of other infections was higher in the chemotherapy alone group (37.9%) versus the Blincyto group (35.2%). No differences in grade 4 or 5 (life-threatening to fatal) side effects were observed between the randomized trial groups.
No deaths were reported during Blincyto cycles, and no deaths were attributed to Blincyto in randomly assigned patients.
“Overall, our results demonstrate that Blincyto added to chemotherapy represents a new treatment standard for most patients with NCI standard-risk B-ALL,” Rau said.
More About the AALL1731 Study
In AALL1731, groups A and C enrolled standard risk-average patients and standard risk-high patients, respectively, to receive chemotherapy alone. Groups B and D enrolled standard risk-average patients and standard risk-high patients, respectively, to receive standard consolidation chemotherapy followed by the first cycle of Blincyto, the second cycle of Blincyto and maintenance chemotherapy.
Overall, clinical, demographic and disease characteristics were balanced across the two risk categories. The median age of patients was 4.3 years old and the majority of patients were boys (52.6%). Hispanic patients comprised 25.8% of the population, and 5.6% of patients were non-Hispanic Black.
“Our standard risk-favorable patients are known to have an excellent survival with standard chemotherapy alone, and thus they were nonrandomly assigned to standard treatment,” Rau added.
Patients classified as standard risk-high were further arranged according to MRD status at the end of the consolidation phase per flow cytometric analysis of bone marrow.
The trial’s primary objective was DFS and other key exploratory objectives included the duration of overall survival, relapse and safety. The data cutoff for the current analysis was June 30, 2024.
Of note, in June 2024, Blincyto was approved by the Food and Drug Administration for the treatment of adult and pediatric patients at least 1 month of age with CD19-positive, Ph-negative, B-ALL in the consolidation phase, regardless of MRD status.
Reference:
“Blinatumomab added to chemotherapy improves disease-free survival in newly diagnosed NCI standard risk pediatric B-acute lymphoblastic leukemia: results from the randomized Children’s Oncology Group” by Dr. S. Gupta, et al. The New England Journal of Medicine.
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