An immunotherapy has demonstrated its safety and efficacy in combating acute lymphoblastic leukemia (ALL) – the most common pediatric cancer – in infants, in a phase 2 clinical trial involving 30 children with an aggressive form of this disease who received immunotherapy with the medicine blinatumomab together with the usual chemotherapy treatment. Results published in the New England Journal of Medicine showed that the survival rate increased significantly – from 66% to 93% – with fewer side effects.
Intensive chemotherapy is effective in half of babies with this type of leukemia, but in the other half the disease recurs within two years, or patients die from it or from adverse effects of treatment. 90% of recurrences occur within two years of treatment.
The new research has been led from the Princess Máxima Center for Pediatric Oncology in the Netherlands and was carried out in nine countries between 2018 and 2021 in babies under one year of age with a specific characteristic in leukemia cells – a rearrangement of the KMT2A gene– which leads to an aggressive form of ALL with a very poor prognosis.
“It is great to see that we have made so much progress for babies with ALL – adding immunotherapy to chemotherapy leads to much better survival and fewer side effects”
Blinatumomab binds to cancer cells on the one hand and immune cells on the other, allowing the immune cells to connect with and kill the leukemia cells. This immunotherapy is already given to some adults and older children with ALL, but it was not known if it would be well tolerated and effective in infants. The children in the study received blinatumomab along with standard chemotherapy treatment – called the Interfant-06 protocol – and the researchers compared the results obtained with those of 214 children who had been treated in previous years with standard therapy alone.
93% of babies lived two years after leukemia diagnosis
The survival rate of babies who received one month of immunotherapy in addition to chemotherapy was significantly improved, with 93% of them still alive two years after diagnosis, compared to 66% of children who had been treated with chemotherapy alone, which puts the survival of infants with a KMT2A rearrangement in their leukemia cells on par with the average survival of older children with this type of blood cancer.
Within two years of diagnosis, 18% of babies treated with blinatumomab had a recurrence of cancer or died from their cause, which is also a significant improvement compared to babies treated with the Interfant-06 protocol alone, as 51% of them had a disease recurrence or died during the two-year treatment with chemotherapy.
Dr. Inge van der Sluis, a pediatric oncologist and clinical pharmacologist at the Princess Máxima Center, said: “It’s fantastic to see that we have made so much progress for babies with ALL: the addition of immunotherapy to chemotherapy leads to much better survival and fewer side effects. We already knew about this immunotherapy from studies in other groups of patients. This is the first time we have tried blinatumomab as a first-line treatment, and for the first time in children this young.”
“This was a small study, but with a clear enough result that all babies with this form of leukemia now receive 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 if babies benefit from two cycles of blinatumomab and a reduction in chemotherapy to further improve their quality of life.”
Dr. Rob Pieters, medical director and pediatric oncologist at the Princess Máxima Center, explains that “infants with leukemia often have a recurrence early in treatment. That’s why it was important to give immunotherapy right at the start of treatment. It is wonderful to see that this is working so well and that we are implementing the incorporation of immunotherapy into global standard treatment immediately.”
In the opinion of Luis Álvarez-Vallina, Head of the H12O/CNIO Mixed Cancer Immunotherapy Unit (12 de Octubre University Hospital/National Cancer Research Center), and as he told SMC Spain, “the follow-up period is short, but the clinical results are spectacular, with a disease-free survival at two years of 81.6%, compared to 49.4% with conventional treatment”.
“Blinatumomab has demonstrated its efficacy in different types of B neoplasms since its initial approval in 2014. This work demonstrates the potential of bispecific antibodies in a type of pediatric leukemia with a very poor prognosis, but in my opinion reaffirms the therapeutic validity of the “T-Redirect” strategies, which are the basis of the next revolution in cancer immunotherapy”, he concludes.
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