400mg imatinib as good as 800mg for 10 year CML survival

Published: 23 Jun 2017

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Prof Rüdiger Hehlmann - European LeukemiaNet, Mannheim, Germany

Prof Hehlmann speaks with ecancer at EHA 2017 about the 10 year survival data of patients receiving imatinib at 400mg or 800mg, after or in combination with IFN or with AraC.

With no significant difference between survival at 10 years for patients on 400mg or 800mg of imatinib, both at 80% and most deaths occurring due to non-disease related reasons, Prof Hehlmann describes life expectancy for patients with CML as "not even living the disease, it is as good as cured".

He notes the quicker response to higher doses of imatinib post-diagnosis, but given the non-superiority for long term survival and greater short-term potency of second generation TKIs, Prof Hehlmann finds no reason for the higher dose.

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

The German CML Study Group is doing randomised treatment optimisation studies for 35 years and we have been continuously in various randomised studies trying to improve survival with CML. CML study 4, that means a treatment optimisation study with imatinib, is the last one in the series of these trials.

And how did it work out?

It was full of surprises. The first surprise was that although doubling the dose of imatinib resulted in faster and earlier responses after ten years there was no survival difference. The second surprise was that currently the causes of death are more frequently due to other causes and patients with CML rarely, only in 5% of cases, die of CML. So what that means is that currently what you need to manage CML patients is more the expertise of a good general internist than that of a haematologist.

A life of living with cancer, managing cancer rather than the death sentence it was?

I wouldn’t put it on that line because with CML we are not really living with cancer. You don’t notice anything and you might just as well be cured without knowing because you can stop imatinib treatment in about half of the cases and there is no relapse. This is now a very hot topic, actually, and also at this congress a variety of presentations on treatment-free remissions. That means stop tyrosine kinase inhibitors are discussed and presented.

Can I just ask, for the other groups who are assessing imatinib 400mg versus 800mg versus the other drugs as well?

None of these arms provided a survival advantage and only imatinib 800mg, doubling the dose, provided a faster response similar to second generation tyrosine kinase inhibitors. So these results of no survival advantage over imatinib 400mg is not really new because we had data like that published last year with second generation tyrosine kinase inhibitors. It was only five years but they did not detect any survival difference between imatinib and second generation TKIs although also there the responses were much earlier and faster with second generation TKIs. So that means that the response, time to response, is not a surrogate marker for survival. That was the assumption, that faster response, earlier response, indicates a survival advantage. We all thought that this is so but it is not. So we all were deceived.

If ten year survival is no different are we just chasing quicker responses now? Is that where research is heading?

What we learned from that is that quicker responses are not meaningful for a better survival. The reason probably is that survival with imatinib at 400mg is so good at 83% after ten years, that means if you do a relative survival, that means that if you compare the survival of these CML patients with that of the general population, you end up with a survival of something like 94% relative survival. That means if you then add up this 5% that still die of CML that makes pretty much the 100%. That means there is no option anymore to improve survival with CML unless you really cut down on the progression rate of CML and on the progression to blast crisis. If you do that then you may be better but we have examples on that like, for instance, with ponatinib. That treats blast crisis and also treats very resistant mutations but there you have the adverse effects so patients die of vascular problems. That means there it starts to become a deal between Scylla and Charybdis, if you know this example, - you either die of blast crisis or you die of vascular side effects. So this is really a difficult situation right now but the baseline is that imatinib is such a good drug, I proposed at an educational at ASCO recently that actually Novartis should get the Nobel Prize for this wonderful drug.

I’m sure they’d be very happy to have that.

Yes, well the problem is they don’t give Nobel Prizes to companies. But this is really something. I’m not aware of any other drug in cancer treatment with such a high efficiency and such a low adverse effects rate.

I would ask where can we go from there but it seems like, like you say, you’ve effectively got a cure.

For the time being we are there.