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Will immunotherapy become first line for childhood ALL?

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Professor Owen Smith CBE

Professor of Paediatric and Adolescent Medicine, University College Dublin

Intensive research and discovery over the last 75 years have pushed overall survival rates in childhood acute lymphoblastic leukaemia up to around 90% – but the cure has come at a cost.

Personalised medicine is the key to reducing the long- and short-term impact for the purpose of cancer treatment on children with acute lymphoblastic leukaemia (ALL).

That’s according to Professor Owen Smith CBE, Professor of Paediatric and Adolescent Medicine at University College Dublin, who says as a result a combination of drug discoveries and risk stratification from the 1940s onwards resulted in event-free survival rates of 87% by the early 2000s.

“But there is a price, and that’s the long- and short-term side-effects. Multi-agent chemotherapy is not very nice as a significant number of these patients experience life-threatening toxicities. Then we started to notice there was a chronicity to survivorship as well: bone disease, heart disease, secondary cancers and neurotoxicity.

“We want all of our patients to grow up and have their own children and to do all of those things that you and I can do,” says.

Personalised antibody therapies to tackle ALL

That’s where new, personalised treatments such as antibody and chimeric antigen receptor T-cell (CAR-T) therapies come in.

Developed thanks to our deeper understanding of the underlying biology of ALL, two new antibody therapies each target a separate specific surface antigens on the leukaemia cells. CAR-T therapy genetically modifies the patients’ own T-cells and returns them to the body to fight the cancer cells.

Crucially, they do not appear to have the same long-term side effect profile as multi-agent chemotherapy.

CAR-T therapy in Ireland will become the new normal

While the antibodies are currently only funded for relapsed or refractory disease and CAR-T therapy in Ireland has not yet received the green light for funding, Professor Smith believes they will soon become the mainstay of first line treatment.

“I firmly believe that, in the next five to ten years, we’re going to be introducing antibodies and CAR-T upfront for standard risk patients. As can be seen, the only thing that’s stopping us from doing that at the moment is the cost.”

Cost is the only barrier to CAR-T therapy in Ireland becoming standard

However, “as with new technologies, as they get better, the price plummets. It took 13 years and $3 billon to sequence the human genome in 2013, but I could sequence your genome tomorrow for €1,000,” Professor Owen Smith says.

Ultimately, these new breakthrough treatments will change the landscape of ALL treatment, he concludes, pushing up survival while reducing toxicity.

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