Dasatinib vs imatinib for paediatric Ph ALL

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Published: 12 Dec 2019
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Dr Ching-Hon Pui - St Jude's Children's Research Hospital, Memphis, USA

Dr Pui talks to ecancer at ASH 2019 about his study to determine whether dasatinib given at 80 mg/m2 is more effective than imatinib at 300 mg/m2 to improve event-free survival of children with Philadelphia chromosome-positive ALL, in the context of intensive chemotherapy without prophylactic cranial irradiation.

225 patients were studied with a median follow-up of 26.1 months (IQR 16.3-34.1), the 4-year event-free survival rate was 71.0% (95% CI 56.2-89.6) in the dasatinib group and 48.9% (95% CI 32.0-74.5, p=0.005) in the imatinib group (hazard ratio 2.36, 95% CI 1.27-4.40, p=0.007).

The 4-year cumulative risk of any relapse was 19.8% (95% CI 4.2-35.4) in the dasatinib group and 34.4% (95% CI 15.6-53.2) in the imatinib group (p=0.01), while the 4-year cumulative risk of an isolated central-nervous-system relapse was 2.7% (95% CI 0.0-8.1) in the dasatinib group and 8.4% (95% CI -1.2-15.6) in the imatinib group (p=0.06).

There were no significant differences in the frequency of severe toxicities between the two treatment groups.

Intensive chemotherapy including dasatinib at 80 mg/m2 per day yielded superior results in the treatment of Philadelphia chromosome-positive ALL compared to imatinib at 300 mg/m2 per day and provided excellent control of central-nervous-system leukaemia without the use of prophylactic cranial irradiation.

ecancer's filming has been kindly supported by Amgen through the ecancer Global Foundation. ecancer is editorially independent and there is no influence over content.

Philadelphia chromosome positive leukaemia remains one of the worst kinds of leukaemia in children. Dasatinib is a second generation tyrosine kinase inhibitor which is available for over ten years. Because of lack of patients no study group can have enough patients to do a randomised trial. The preliminary study at St Jude’s showed that this is possibly a good drug, we probably can cure most of them without the use of prophylactic cranial radiation.

Because China has lots of patients so we approached our colleagues in China to do a randomised trial to see if dasatinib is superior to the first generation tyrosine kinase inhibitors. Over four years we randomised almost 200 patients. We are happy to show that dasatinib is indeed superior to the first generation drugs. More importantly, we can spare all the patients from getting prophylactic cranial irradiation which is still commonly used for this type of leukaemia.

This trial showed that dasatinib should become the standard of care for children with Philadelphia chromosome positive acute lymphoblastic leukaemia. Having said that, there is still plenty of room for improvement because we only can cure 65-70% of the patients. This is totally not acceptable – we want to cure patients over 90% or we hope to cure all of them so there’s still a lot of room for improvement.

For the next step we really need to combine the whole effort so we need to do a study so that we can get enough patients to do a good trial so that we can compare so we can put the outcome to over 90-100%.

This randomised trial benefits patients not only in China, not only in the US but around the world because dasatinib should be the standard of care for all children around the world with this type of leukaemia. So the next step we really need to do a global study to test even newer novel drugs. So perhaps combined with additional novel drugs we can further push the outcome to 90%, better yet to cure them all.