Short-Term Follow-up of Blinatumomab in Children with B-Cell Precursor Acute Lymphoblastic Leukemia：Study of a Single Center from China

Background: Acute lymphoblastic leukemia (ALL) is the most common hematologic disorders in children. The 5 years overall survival (OS) has reached more than 90%, but still 20% of patients relapsed. Positive of microscopic residual disease (MRD⁺) is the important factors for pediatric ALL. Blinatumomab is a combination of CD3 and CD19 bispecific antibody. Previous studies have shown that it has a significant advantage in improving the efficacy and survival of refractory /relapsed (R/R) ALL and MRD⁺ patients. Blinatumomab has been approved in China for R/R ALL indications in adults and children respectively since Aug 2021 and Apr 2022. So far, there is a lack of research data on ALL in Chinese children. This study mainly discusses the short-term efficacy and safety of Blinatumomab for R/R ALL and MRD⁺ of children with B-ALL in China.

Methods: We collected the patients' information of children with R/R or MRD⁺ B-ALL treated with blinatumomab from Aug 2021 to Jun 2022 in our single institute from China. Retrospectively analyzed were carried out for the short-term efficacy and safety.

Results: since Aug 2021, blinatumomab has been introduced to China. 13 cases were enrolled in this study, including R/R ALL 6 cases and MRD ⁺ ALL 7 cases, the median onset age of 9.5 (range 5-14) years old, male: Female =8:5, in the R/R-ALL group, there was 1 case of sustained no remission (NR), 1 case of very early recurrence(<18 months) and 1 case of late recurrence(≥36 months), and 3 cases of early recurrence, ALL of which were isolated bone marrow recurrence for the first time. 3 cases were treated with reinduction chemotherapy before blinatumomab. The mean proportion of blast cells in bone marrow (BM) prior therapy was 34.3 (range 0-96) %. The mean flow cytometry MRD was 30.26 (range 0.11-78.3) %. 3 patients were with no dose uphill due to low tumor load. 3 patients were given uphill 5ug/m² qd d1-7, 15ug/m² d8-28, of which 1 was treated for 14 days and 2 for 21 days. The investigator evaluated the efficacy of the treatment and stopped the drug. After treatment, bone marrow morphology was complete response (CR) in 3 cases, of which 2 cases had MRD negative (MRD^-), the Cytokine release syndrome (CRS) incidence was 83.3%, 2 cases had CRS grade 2, 3 cases CRS grade 1, and the main manifestations were fever and hypotension. The levels of cytokines were significantly increased in patients with CRS, especially in IL-6, IL-8 and IL-10. The median level of IL-6 in CRS was 3081.8 (range 12.6-10405.0). IL-8 214.5 (range 23-408.0) and IL-10 377.7 (range 6.7-1398.0) (normal value ≤ 4.91) were significantly higher than those before blinatumomab and after CRS disappeared. In the MRD⁺ ALL group, there were 2 cases of chemotherapy drug intolerance, 1 case of inadequate treatment, and 4 cases of continuous MRD⁺ after standard chemotherapy. In MRD⁺ALL group, the BM of All cases were CR before treatment, the mean flow MRD value was 0.63 (range 0.01-4.00) %, the blinatumomab was 15ug/m² (weight < 45kg) or 28ug (weight ≥45kg) for 7-28 days. After treatment, the MRD of 7 cases were all turned negative and the incidence of CRS was 71%. All of which were CRS

grade I. When CRS occurs, the median IL-6 level is 76.4 (range 4.4-271.0) (normal value ≤ 5.3), IL-8 18.7 (range 8.0-35.5) (normal value ≤ 20.6), IL-10 447.3 (range 8.9-2570.0) (normal value ≤ 4.91)

Conclusion: The CR rate of R/R pediatric B-ALL was 50%, the MRD^- rate was 67%. The rate of MRD turned negative was 100% in MRD⁺ B-ALL group. In this study, the tolerance of blinatumomab in children with B-ALL was good, and the incidence of CRS was about grade 1/2, and no neurological complications occurred. The occurrence of CRS was mainly caused by the increase of cytokines, especially IL-6, IL-8 and IL-10. The IL-6 of CRS in R/R ALL group was significantly higher than that in MRD⁺ ALL (Fig.12.798, P=0.007).

No relevant conflicts of interest to declare.