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Outcomes for Australian children with relapsed/refractory acute lymphoblastic leukaemia treated with blinatumomab
Rosemary Sutton1,2, Luciano Dalla Pozza3, Seong Lin Khaw4
1Molecular Diagnostics, Children's Cancer Institute, Sydney, New South Wales, Australia.
Insights
Blinatumomab shows promise for children with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), achieving a 58% minimal residual disease response. Survival outcomes varied, with some patients proceeding to stem cell transplant or CAR T-cell therapy.
Area of Science:
- Pediatric Oncology
- Hematology
- Immunotherapy
Background:
- Relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) in children presents significant treatment challenges.
- High-risk genetics further complicate treatment outcomes for pediatric B-ALL.
- Blinatumomab offers a targeted immunotherapy approach for B-ALL.
Purpose of the Study:
- To evaluate the Australian experience with blinatumomab in pediatric B-ALL.
- To assess response rates, survival, and transplant eligibility post-blinatumomab.
- To identify prognostic factors influencing outcomes in relapsed/refractory B-ALL.
Main Methods:
- Retrospective analysis of 24 children with relapsed/refractory B-ALL treated with blinatumomab.
- Evaluation of minimal residual disease (MRD) response rates.
- Assessment of progression-free survival (PFS) and overall survival (OS).
- Analysis of subsequent treatments including hematopoietic stem cell transplant (HSCT) and CAR T-cell therapy.
Main Results:
- A 58% MRD response rate was observed.
- Two-year PFS was 39% and 2-year OS was 63%.
- 83% of patients proceeded to HSCT.
- Prior blinatumomab exposure did not preclude subsequent CAR T-cell therapy.
- Inferior PFS was linked to MRD positivity and KMT2A rearrangement in infants.
Conclusions:
- Blinatumomab demonstrates efficacy in a subset of children with relapsed/refractory B-ALL.
- Treatment outcomes are influenced by factors including MRD status and genetic profile.
- Blinatumomab can serve as a bridge to further intensive therapies like HSCT and CAR T-cell therapy.
Abstract:
We report on the Australian experience of blinatumomab for treatment of 24 children with relapsed/refractory precursor B-cell acute lymphoblastic leukaemia (B-ALL) and high-risk genetics, resulting in a minimal residual disease (MRD) response rate of 58%, 2-year progression-free survival (PFS) of 39% and 2-year overall survival of 63%. In total, 83% (n = 20/24) proceeded to haematopoietic stem cell transplant, directly after blinatumomab (n = 12) or following additional salvage therapy (n = 8). Four patients successfully received CD19-directed chimeric antigen receptor T-cell therapy despite prior blinatumomab exposure. Inferior 2-year PFS was associated with MRD positivity (20%, n = 15) and in KMT2A-rearranged infants (15%, n = 9). Our findings highlight that not all children with relapsed/refractory B-ALL respond to blinatumomab and factors such as blast genotype may affect prognosis.
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