New Risk-Stratification Tool Predicts Relapse After Blinatumomab in Childhood ALL

Traditional relapse predictors were developed largely in chemotherapy-based treatment settings and may not fully reflect risk in patients receiving newer immunotherapy-based regimens. This can complicate treatment planning and decisions about follow-up. Researchers now report new predictors of relapse in children and young people with B-cell acute lymphoblastic leukemia treated with blinatumomab.

Newcastle University and Great Ormond Street Hospital identified relapse risk factors in a U.K.-wide cohort of young patients receiving blinatumomab as a replacement for parts of standard chemotherapy. The findings led to the development of BlinPredict, a risk-stratification tool that combines early treatment response with genetic information to identify patients at higher risk of relapse after this immunotherapy-based approach.

The national study included more than 200 young patients with B-cell acute lymphoblastic leukemia treated across 24 centers in the U.K. and Ireland. Treatment response data were collected through regional laboratories, while genetic testing, including whole-genome sequencing, was performed through NHS Genomics Laboratory Hubs and analyzed centrally.

The study found that several relapse risk factors traditionally used in childhood acute lymphoblastic leukemia were no longer reliable in patients receiving blinatumomab. These included age, white blood cell count, high-risk genetic features, and measurable residual disease before treatment. Instead, the strongest predictor of future relapse was the amount of leukemia remaining after the first cycle of blinatumomab.

The researchers also identified IKZF1plus and DUX4-rearranged leukemia as genetic subtypes associated with poorer treatment response and higher relapse risk. The findings were published in Blood Advances. Future work will focus on understanding why some leukemias are resistant to blinatumomab and on identifying risk factors in other patient groups, including adults with acute lymphoblastic leukemia.

“Blinatumomab is transforming the treatment of childhood acute lymphoblastic leukemia, but until now we did not know whether the risk factors used for decades in chemotherapy-based treatment still applied. Our findings show that many of them do not. Instead, a child's early response to blinatumomab, together with specific genetic features of their leukemia, provides a much more accurate picture of relapse risk,” said Anthony Moorman, joint lead author from Newcastle University.

“This research will help clinicians identify which patients are likely to do exceptionally well with reduced chemotherapy and which will require a different treatment approach. Reducing exposure to chemotherapy has the potential to lessen side effects and improve quality of life, while ensuring that higher-risk patients receive the treatment they need,” added Moorman.

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