Data from a multicenter, randomized phase 3 study ( 20120215 ) evaluating the efficacy, safety and tolerability of Blinatumomab ( Blincyto ) compared with consolidation chemotherapy before allogeneic hematopoietic stem cell transplantation ( alloHSCT ) in pediatric patients with high-risk first-relapse B-cell precursor acute lymphoblastic leukemia ( B-ALL ) were published in JAMA ( Journal of the American Medical Association ).

Blinatumomab has demonstrated significantly prolonged event-free survival ( events were defined by relapse, death, second malignancy, or failure to achieve complete remission ) compared with chemotherapy.
After a median of 22.4 months follow-up, 69% of patients treated with Blinatumomab were alive and event-free compared with 43% of patients treated with chemotherapy.
Additionally, following treatment with Blinatumomab, 93% of patients with minimal residual disease ( MRD ) at baseline achieved MRD negative remission compared with 24% of patients treated with chemotherapy.
The 36-month overall survival ( OS ) estimate in the Blinatumomab group was 81.1% versus 55.8% in the chemotherapy group, and the median overall survival has not been met.

In the Blinatumomab group versus the chemotherapy group, the incidence of serious adverse events was 24.1% vs. 43.1%, respectively, and the incidence of adverse events of grade 3 or higher was 57.4% vs. 82.4% respectively.
No fatal adverse events were reported.
The most common adverse events in the Blinatumomab treatment arm were pyrexia ( 81.5% ), nausea ( 40.7% ), headache ( 35.2% ), stomatitis ( 35.2% ) and vomiting ( 29.6% ).

Blinatumomab is a BiTE ( bispecific T-cell engager ) immuno-oncology therapy that targets CD19 surface antigens on B cells.
BiTE molecules fight cancer by helping the body's immune system detect and target malignant cells by engaging T cells to cancer cells. By bringing T cells near cancer cells, the T cells can inject toxins and trigger cancer cell death ( apoptosis ).

Results from the Children's Oncology Group ( COG ) phase 3 study ( AALL1331 ) evaluating Blinatumomab in children, adolescents, and young adults with first-relapse B-ALL have also been published in JAMA.

In both studies, treatment with Blinatumomab resulted in less severe toxicities and higher rates of MRD remission.

20120215 study

20120215 study is a phase 3 open-label, multicenter, randomized, controlled trial evaluating event-free survival after treatment with Blinatumomab compared with standard of care consolidation chemotherapy in pediatric patients with high-risk first-relapse B-cell ALL.
Study enrollment was terminated early in September 2019 due to encouraging efficacy in the Blinatumomab arm and was based on a recommendation from the DMC ( Independent Data Monitoring Committee ) in accordance with a prespecified stopping rule.
Key secondary endpoints included overall survival and MRD response, adverse effects, 100-day mortality after alloHSCT, incidence of anti-Blinatumomab antibody formation, cumulative incidence of relapse.

COG AALL1331 study

COG AALL1331 study is a risk-stratified, randomized, phase 3 trial of Blinatumomab in first relapse of pediatric B-ALL to evaluate disease-free survival ( DFS ) of high-risk ( HR ) and intermediate-risk ( IR ) relapsed B-ALL patients who are randomized following induction block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of Blinatumomab.
It has also compared the DFS of low risk ( LR ) relapse B-ALL patients who are randomized following block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus Blinatumomab.
Key secondary endpoints include overall survival of high-risk, intermediate-risk and low-risk relapsed B-ALL patients. ( Xagena_2021 )

Source: Amgen, 2021

Xagena_Medicine_2021