Frontline therapy of ALL

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Published: 23 Jan 2020
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Prof Hervé Dombret - University Paris Diderot, Paris, France

Prof Hervé Dombret speaks to ecancer at the 2020 ALL Assembly meeting about the frontline therapy options for ALL.

He explains that it is important to understand that the disease is biologically very different across the different age groups and that these groups react differently to treatments.

Prof Dombret highlights the treatment of children with relapsed refractory disease as one of the most challenging areas at present. 

 

The session, we will have three speakers – one for children, one for adolescents and young adults and one for the older ALL patients. What is important to realise is that the disease is not the same across the different ages, there are some biological subsets of the disease that are very different, the distribution of the subsets is very different in children as compared to the older adults. So that’s maybe one of the reasons why even if we can deliver the same treatment to older patients as compared to younger or to children, which is not the case because older adults cannot tolerate very intensive chemotherapy, but even in that case we would not produce the same result because the disease is not the same. In the older age there are many more resistant subgroups of the disease, subsets resistance to standard chemo.

So we are currently at the limit of the use and results associated with standard chemotherapy and we need new drugs. The good thing is that we do have these drugs now and the next challenge is to move these drugs from the relapsed refractory setting to the frontline setting.

Would you say that the treatment of either adult ALL or paediatric ALL is more challenging than the other at present?

I would say that for paediatricians the most important problem at the present time is how to treat those children who relapse with the disease. So the most important issue is to treat relapsed refractory disease. In the adult setting the most important issue is to treat high risk patients, those patients with ALL with a higher risk of relapse frontline. So it’s not exactly the same issues and the same way to deal with these issues.

Where do you see the treatment of adult and paediatric ALL 5 years from now?

For paediatricians the problem is what is the optimal treatment for relapsed refractory disease. We have the same issue but frontline but basically that’s the same issue and we will use the same tools and the same new drugs to address these two issues. That’s the introduction of immunotherapy to treat relapsed refractory disease in children and to treat frontline disease in the adults. How this immunotherapy is including CAR T-cells but also bispecific antibody-drug conjugates could allow us to reduce, again, the incidence of transplantation because transplantation is quite aggressive procedures associated with long-term complications and problems. So this is the most important question for me at the present time is how these new drugs will allow us to improve the results and the survival of these high risk patients, relapsed, refractory, mostly in children patient subsets at higher risk of relapse, mostly in adults.

The area, it will be addressed by Oliver Ottmann from Cardiff University, the area of Philadelphia chromosome positive ALL. It’s quite exciting because in that subgroup, which is very rare in children but very frequent after 40-45 years of age, in that subset we have new immunotherapies but we also have more and more potent tyrosine kinase inhibitors to treat these patients. So the next step, the dream, is to treat these patients only with immunotherapy and tyrosine kinase inhibitors, no chemotherapy, no stem cell transplantation. Very interesting preliminary results on the basis of that combination, for instance blinatumomab plus ponatinib, are coming up and that’s really exciting for the near future.