The addition of blinatumomab to chemotherapy may improve disease-free survival in pediatric patients newly diagnosed with National Cancer Institute (NCI) standard-risk B-cell acute lymphoblastic leukemia (ALL) at average or high risk of relapse, according to new findings presented by Rau et al at the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 1) and simultaneously published by Gupta et al in The New England Journal of Medicine.
Background
“Relapsed ALL remains a major cause of pediatric cancer mortality, with nearly half of the relapses occurring in [patients] with standard-risk B-[cell] ALL,” stressed co–lead study author Rachel E. Rau, MD, Associate Professor of Pediatrics at the University of Washington, Co-Chair of the Children's Oncology Group AALL1731 study, and a pediatric hematologist-oncologist at Seattle Children's Hospital. “These findings underscore the progress made with blinatumomab in preventing relapse and support its role as a critical addition to current therapeutic strategies,” she continued.
Blinatumomab is a first-in-class bispecific T-cell engager immuno-oncology therapy that targets CD19 surface antigens on B cells. These molecules are designed to fight cancer cells by helping the body's immune system detect and target malignant cells and engaging T cells to cancer cells. By bringing T cells near cancer cells, the T cells can inject toxins and trigger apoptosis.
“Over the last decade, [blinatumomab] has reshaped the treatment landscape for B-[cell] ALL, offering a critical lifeline for thousands of adult and pediatric patients,” explained Jay Bradner, MD, Executive Vice President of Research and Development and Chief Scientific Officer at Amgen.
Study Methods and Results
In the new phase III AALL1731 study (ClinicalTrials.gov identifier NCT03914625), researchers assigned patients with standard-risk B-cell ALL to receive either blinatumomab plus chemotherapy or chemotherapy alone.
Based on the results of the first prespecified interim analysis for efficacy, the study met its primary endpoint of disease-free survival, and study randomization was terminated early after the data and safety monitoring committee observed benefit in the patients receiving blinatumomab compared with those receiving chemotherapy alone. Overall, the 3-year disease-free survival rate was 96% among the patients treated with blinatumomab plus chemotherapy vs 87.9% among those treated with chemotherapy alone (hazard ratio [HR] = 0.39, 95% confidence interval [CI] = 0.24–0.64)—indicating a 61% reduction in the risk of disease relapse, secondary malignant neoplasm, or remission death with the use of blinatumomab. At 3 years, a larger number of patients in the blinatumomab plus chemotherapy group remained alive and cancer free compared with those in the chemotherapy alone group.
The addition of blinatumomab to chemotherapy in standard-risk patients resulted in outcomes comparable to those previously achieved in only the most favorable pediatric risk subsets. Among standard-risk–average patients, the 3-year disease-free survival rate was 97.5% among patients treated with blinatumomab plus chemotherapy compared with 90.2% among those treated with chemotherapy alone (HR = 0.33, 95% CI = 0.15–0.69). For standard risk–high patients, the 3-year disease-free survival rate was 94.1% among the patients in the combination treatment group vs 84.8% among those in the chemotherapy alone group (HR = 0.45, 95% CI = 0.24–0.85).
The safety results were consistent with the known safety profile of blinatumomab. The drug demonstrated a positive balance of benefits and risks, with only 0.3% of first courses associated with grade 3 or greater cytokine release syndrome and 0.7% with seizures. A higher risk of infections was observed in the blinatumomab plus chemotherapy group.
Conclusions
“The AALL1731 study results are truly practice-changing, further solidifying blinatumomab's role as the standard of care for a large number of [pediatric patients] with B-[cell] ALL,” indicated co–lead study author Sumit Gupta, MD, PhD, FRCPC, Associate Professor of Pediatrics at the University of Toronto, Co-Chair of the Children's Oncology Group AALL1731 study, and an oncologist and clinician investigator in the Division of Haematology/Oncology at The Hospital for Sick Children. “These breakthrough data showing a significant improvement in disease-free survival are poised to bring substantial clinical value to [patients] with newly diagnosed B-[cell] ALL,” he highlighted.
The findings provided early evidence supporting blinatumomab for use in the consolidation phase in patients with newly diagnosed pediatric Philadelphia chromosome–negative B-cell ALL and may help redefine the standard of care in both adult and pediatric patients, as young as 1 month old, regardless of measurable residual disease status. The results of the study further establish blinatumomab as a versatile first-line consolidation therapy across all ages and treatment backbones.
“These powerful new data leave us little doubt about the profound impact of this medicine for a large number of [pediatric patients] affected by this disease. We are grateful to the Children's Oncology Group along with the patients, families, and clinical teams for their dedication and partnership in advancing this critical study to improve the lives of [patients] with cancer,” Dr. Bradner stated.
The NCI's Cancer Therapy Evaluation Program expects to share data with the U.S. Food and Drug Administration as part of its ongoing communications related to the trial.
Disclosure: The research in this study was sponsored by the NCI's Cancer Therapy Evaluation Program. For full disclosures of the study authors, visit ash.confex.com and nejm.org.
