BLINATUMOMAB TREATMENT OUTCOMES IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA PATIENTS: THE DATA FROM TÜRKİYE

Background:Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in children. Significant progress has been made in the treatment of pediatric ALL, with long-term survival exceeding 85%. Nevertheless, approximately 15-20% of children with ALL experience relapse after standard first-line chemotherapy. Blinatumomab is a targeted therapy successfully used to achieve remission in these children. It is a bispecific T cell-binding (BiTE) antibody that induces an antitumor response by pairing CD19-positive malignant B cells with cytotoxic T lymphocytes. In clinical practice, it offers an effective option, particularly in infant B-ALL patients who are KMT2A positive, in pediatric precursor B-ALL (pre-B ALL) patients resistant to chemotherapy and as bridging therapy to stem cell transplantation (SCT) in cases with MRD positivity.

Aims: The aim of this study was to evaluate treatment responses and survival rates in childhood pre-B ALL patients treated with blinatumomab.

Methods: This study included children diagnosed with CD-19-positive B-ALL in Türkiye between January 1, 2014, and December 30, 2024.

Results: 147 patients diagnosed with CD-19-positive ALL were included in the study. Of the 10 children diagnosed with infant ALL, 2 received blinatumomab due to minimal residual disease (MRD) positivity and refractory disease, while 8 received it according to the protocol. Additionally, patients were divided into three groups based on the stage of treatment at which they received blinatumomab therapy:

Group A: Patients receiving Blinatumomab in complete remission 1 with positive MRD or overt blasts(CR1) (n=44)

Group B: Patients receiving Blinatumomab after relapse (n=67)

Group C: Patients receiving Blinatumomab due to relapse after HSCT (n=36).

The median (min-max) age of patients at initial diagnosis was 4.25 years, 4.91 years, and 6.75 years in groups A, B, and C, respectively. The majority of children (57%) were in the high-risk group (HRG) at initial diagnosis. Blinatumomab was administered in courses ranging from 1 to 3 cycles. HSCT was performed in 52%, 79%, and 39% of groups A, B, and C, respectively.

There were a total of 33 patients with M3 (blast ≥25%) bone marrow before Blinatumomab therapy. The distribution of these children was as follows: Group A 7% (n=3), Group B 25% (n=17), and Group C 36% (n=13).

In total, 54 out of 147 patients (37%) died. Mortality rates according to groups were found to be 9%, 43%, and 58% in groups A, B, and C, respectively (p<0.05). Children with M3 bone marrow in each group had significantly lower event-free survival (EFS) rates after induction compared to those with M1 and M2 bone marrow (p<0.05).

The 5-year overall survival (OS) for the entire cohort was 61%, and event-free survival (EFS) was 55%. Patients in group A had significantly higher OS(89%) and EFS (81%) compared to the others (p<0.05). In group B, the 5-year OS was 63%, and EFS 60%; in group C, OS was 43%, and EFS was 37%.

Summary/Conclusion: The results  showed that administration of blinatumomab in children group A who had positive MRD or blast percentage  less than 25% had the highest OS and EFS rates (p<0.05). Survival rates were significantly reduced in cases of relapse after stem cell transplantation(p<0.05). Therefore, early administration of blinatumomab in the treatment of ALL is crucial, especially in countries with limited resources.