Three quarters of babies with acute lymphoblastic leukemia (ALL) – three babies a year in the Netherlands – have a particular fault in the DNA of their leukemia cells. This so-called KMT2A rearrangement leads to an aggressive form of ALL with a poor prognosis. Despite intensifying chemotherapy, the prognosis for these babies has not improved in recent decades.
Intensive chemotherapy works very well for half of the babies. But in the other half of the children, the disease returned within two years, or children died from the disease or sometimes from the side effects of the therapy.
Immunotherapy with the drug blinatumomab is already offered to some adults and older children with ALL. It was still unclear whether this treatment is also well tolerated and effective in babies. Blinatumomab binds to leukemia cells on one side and to immune cells on the other side. This connects the immune cells to the leukemia cells causing them to be cleared.
International clinical trial
Researchers at the Princess Máxima Center led an international clinical trial looking at the safety and effectiveness of blinatumomab in babies with ALL. Between 2018 and 2021, 30 children in nine countries – of whom nine children in the Netherlands – were treated with blinatumomab. This was added to the existing chemotherapy treatment, the so-called Interfant-06 protocol. The team compared the outcomes with those of 214 children who had been treated in previous years with the Interfant-06 standard therapy: the same treatment, without blinatumomab.
Significant improvement
The survival rate of babies who received one month of immunotherapy in addition to chemotherapy was significantly higher: 93% of them were still alive two years after diagnosis, compared with 66% of children who had only been treated with chemotherapy in the past. This brings the survival of the babies with a KMT2A rearrangement in their leukemia cells to the level of the average survival of older children with this form of blood cancer.
Two years after diagnosis, 18% of babies treated with blinatumomab saw their cancer come back, or died from their disease. This also indicates a strong improvement compared with babies treated within the Interfant-06 protocol, without immunotherapy. In that group, 51% had a recurrence or death during the two-year treatment with chemotherapy.
The results of the international clinical trial were published in the prestigious New England Journal of Medicine. The study was funded by the Princess Máxima Center Foundation and the pharmaceutical company Amgen.
Part of standard treatment
Dr. Inge van der Sluis, pediatric oncologist and clinical pharmacologist at the Princess Máxima Center, led the clinical study. She says: ‘It’s fantastic to see that we have made such progress for babies with ALL: the addition of immunotherapy to chemotherapy leads to much better survival and fewer side effects. We were already familiar with this immunotherapy from studies in other patient groups. This is the first time that we tested blinatumomab as a first-line treatment, and for the first time in such young children.
‘This was a small study, but with a clear enough result that all babies with this form of leukemia are now receiving immunotherapy as part of standard treatment. We want to confirm the effect of blinatumomab in a larger study with more children. We also want to see whether babies benefit from two courses of blinatumomab and a reduction in chemotherapy, in order to improve their quality of life even further.’
The scientific article can be found here: Van der Sluis IM, et al. Blinatumomab Added to Chemotherapy in Infant Lymphoblastic Leukemia. N Engl J Med. 2023 Apr 27;388(17):1572-1581.