EHA 2016
An overview of MCL from EHA 2016
Professor Steven Le Gouill – University Hospital of Nantes, Nantes, France
Professor Simon Rule – Derriford Hospital, Plymouth, UK
SR: Good afternoon, welcome to Copenhagen. I’m Simon Rule, I’m a haematologist from Plymouth in the UK and this is ecancer.tv. Joining me is my good friend and colleague Steven Le Gouill from Nantes in France and we’re here to talk about mantle cell lymphoma. In the first instance, Steve, there was a discussion this morning at EHA in the mantle cell lymphoma session about autologous stem cell transplantation. Of course we’ve got these new drugs that are all very exciting and the conversation at that discussion was what role is autologous transplantation does it have now and potentially in the future with these new drugs coming along.
SLG: It was a very interesting debate and I think it’s very up to date. This is a real question now but I think we all have to keep in mind that autologous stem cell transplantation for a young patient with advanced disease still remains the standard of care outside of clinical trials. I think it’s important to remind this to the audience because we all want to stop to do the transplant front line for patients. We have new drugs, we have new combos of great, great interest and we have the feeling that we could maybe change the way we treat the patients and that autologous stem cell transplant maybe is living its last years as a front line treatment. So the debate this morning was really around this question, it is time or not time to change the treatment and to say that autologous is no longer the treatment. My feeling is that it’s still the recommendation. Surely if you read the expert recommendation it should remain standard of care. For how long, that’s also the question and maybe we will go to a chemo or chemo free, whenever it’s chemo free, but we have to do it step by step, not go too far.
SR: Yes, I think that’s a good point because particularly the issue around chemotherapy. Chemotherapy works.
SLG: Yes it does.
SR: And I think there’s this hype around new drugs and this chemo free, as you say, but your Nordic style protocol or your French approach, half the patients are alive at ten years. This works and if we’re going to challenge that with new drugs we need to know what they deliver in that sort of time span.
SLG: Yes, it’s really these new drugs give very interesting response rates, at least ibrutinib is a very good example and ibrutinib plus rituximab but also R-squared. What we don’t know is how long these patients remain disease free. Of course two or three years but two or three years is no longer enough in mantle cell lymphoma, we need to know what’s going on after five, six years. We all worry about the outcome of the patient when they fail this new therapy and this is what we have to learn from clinical trials and from real life data. Today we know that chemo works, 90% of patients reach complete remission after autologous stem cell transplantation and nearly 70% have MRD negativity in the bone marrow and the blood so it’s a very, very good level of response. Do these new drugs do better with a longer follow up? That’s the question, very important question.
SR: The other thing is do you add new drugs to conventional treatment or do you use new drugs instead of conventional treatment? The conservative approach generally in oncology is you add. I think these drugs are so effective we need to challenge that.
SLG: I agree. If we want to change the paradigm of treatment it’s not by adding, adding, adding some things to chemo otherwise still chemo. If these drugs are so effective then they will have to demonstrate that they are stronger than chemo alone otherwise it’s just another life of chemo and this is not what we are looking for.
SR: Of course the other thing to think about is if you do an autologous stem cell transplant you treat, OK, you’re probably going to give some maintenance afterwards, as you’ve shown, but then you finish, you stop. Patients are off treatment then. On these new drugs potentially they’re on them for a long period of time and there’ll be compliance issues and there are obviously cost issues which you can’t get away from. So it’s not just as simple as one regimen versus another.
SLG: Yes, it’s a good point. Chemotherapy has a beginning and it has an end and then you’re drug free. With this chemo free you never stop the drugs so you’re not drug free, it’s a never ending treatment. So it costs a lot of money and we will see what happens in time when patients will have side effects. Because this is also something we learned from these new drugs is new side effects that we are not used to seeing in haematology or at least that were rare or unexpected. We see a lot of new unexpected side effects with the new drugs.
SR: Yes, exactly right. And then, of course, these drugs do work post-transplant so reserving them to a bit later on may not be a bad thing. It’s how you sequence things, we’re not curing people with autologous stem cell transplantation.
SLG: Maybe we cure some of them. Even if the curve there is no plateau, there are still patients remaining disease free after eight, nine, ten years. Who knows that we didn’t… maybe we have cured some patients. I don’t know, but maybe.
SR: But there are on chemotherapy.
SLG: There are, yes.
SR: The trial we did in the UK of FC versus FCR, some of those patients are disease free at ten years.
SLG: Yes, if you look at the curves of autologous stem cell transplantation in real life, one third of the patients are still disease free more than eight or nine years after treatment. So I don’t know if they are cured or not but they really enjoyed a very long period of time without any treatment which is a really good point, in fact. No need for them to have the new drug for never-ending.
SR: The trouble is we don’t know who they are, do we?
SLG: That’s exactly the point.
SR: That’s the biology, can we pick at the beginning which patients we should treat in one way or another. We’re recognising this indolent subtype but I’m not convinced there’s any real test you can do at diagnosis to predict who those patients are. We watch them and when they progress we treat them as if they were de novo. So we’re not doing anything different in those patients. Biologically they’re clearly different because they don’t progress in the same way.
SLG: This is a very important field of research, to be able to pick out the patients that will respond to this treatment but not to the other one and then to offer to each patient a very adapted, personalised treatment. These new drugs are really a good example of a personalised approach. We have to work on this, on this topic, you’re right. I think there are some patients that do not deserve autologous stem cell and a few chemotherapy will probably give them a very long time period of response while others will really need something else than autologous stem cell because they will never respond to chemo, even intensive chemo. Difficult to know who is who at the beginning of the story. We have some clues, we have some directions to go to but it’s really in daily practice difficult to know. Maybe NGS or new stuff like that will help us.
SR: The other point, and we touched about this earlier, you mentioned it this morning, in myeloma where they’ve got an explosion of new drugs, you add new drug to new drug to new drug, you get better and better and better responses, transplant still stands. So you still need that chemotherapy, that high dose chemotherapy, to presumably kill the cells the new drugs aren’t getting at.
SLG: Yes, still a little bit disappointing, isn’t it, because we expect so much about these kinds of trials. But we have to go back to reality, autologous works and works pretty well. Is it the same in mantle cell, that’s another question.
SR: I think that’s a reasonable place to stop. I think our take home message there is new drugs are very exciting but chemotherapy works and in young patients we know the outcomes are very good. Older patients probably a different ballgame but in young patients chemotherapy works and we should still be using a high dose approach. I think the new drugs are going to find their place but it’s going to be a bit longer in younger patients than older patients.
