Blood Cancer in the Elderly: European Expert Forum, Rome, 19—20 March 2011

Professor Gareth Morgan (Institute of Cancer Research, Sutton, UK)

Benefits of maintenance therapy for multiple myeloma

ecancer.tv continues our look at blood cancers in the elderly here in Rome with Professor Gareth Morgan. Gareth, you’ve just been talking about maintenance therapy in multiple myeloma. Now, what is the importance of maintenance therapy as far as your research has shown?

One of the important new concepts I think in the treatment of myeloma is, once you’ve got a patient into a response, is how do you hold them in that response for a prolonged period of time, with the aim of improving their overall survival. And I think, since the development of the IMiD drugs, which have this very interesting mode of action, which I think modulates the behaviour of the residual myeloma cells when they’re in a remission, I think that we’re starting to see improvement in progression-free survival that translates into overall survival. And the biology underlying all of that is a very productive area that we need to study in more detail.

So there are now hard data on the use of IMiD drugs in maintenance?

Yes, very much so. There are at least three studies that show that if you continue the use of lenalidomide long term that you are able to control the myeloma clone and prevent relapse. And the significance of the data is largely that there is such a big difference between the maintained and non-maintained group that I think this is going to turn into a survival benefit for patients.

And although there is a big variety of agents, a fairly good variety of agents, for induction, in maintenance it’s just the IMiDs that are emerging, is it?

Yes, as we were discussing, there is a historical perspective to all of this. People have tried maintenance drugs in the past, and we’ve used steroids, interferon, alkylating agents, and none of them proved successful, largely because of their side effect profile. But with the IMiD drugs and lenalidomide in particular, it’s got a very favourable side effect profile, which allows you to leave people on it and it doesn’t impact their quality of life. And I think because of this, that we really are starting to see now a resurgence in this idea.

Or although with side effects thalidomide did blaze a trail, didn’t it?

Yes, we’ve done a large study with thalidomide maintenance and part of the issue with it was that patients only managed to stay on it, on average, seven months. So for a maintenance strategy, really you should stay on it until disease progression. But you learn a lot from the study of these older drugs like thalidomide and we can see that any thalidomide exposure is better than no thalidomide exposure.

The very best outcome was when thalidomide was used for induction and maintenance. However if you didn’t get the thalidomide in induction you could use it in maintenance and overcome some of the negative impacts of that omission in presentation.

And so this is a very important lesson about how to use lenalidomide, and also brings up this issue of sequencing of cancer drugs and the therapeutic armamentarium in myeloma has now got much better than it was, and we’re starting to have the ability to select drugs which have a profile good for induction and drugs which have a better profile for maintenance.

Could you give me some idea of just how much extension of life, and progression-free survival, you can get with IMiD maintenance?

It’s very difficult to put a figure on it at this point in time, because the improvement in survival, or progression-free survival at least, has been so good that the lenalidomide-maintained group haven’t hit their medians - we normally talk about a median of this versus a median of that. But in terms of hazard ratio, there’s about an 80% reduction in the risk of relapse which is at a very high p-value, so that makes it very, very significant.

Very exciting indeed. And specifically with respect to older patients, what’s the relevance of all of this, rather than younger patients with multiple myeloma?

So, in younger patients you would try to get them to a transplant and probably now you’d want to give them some form of maintenance, preferably with lenalidomide. And that’s the data from the two studies, the CLGB and the IFM study.

In the elderly group of patients, you have to be a lot more careful about side effect profiles, and so the addition of extra drugs to induction can cause some fallout of patients and similarly, elderly people become very pragmatic about their survival and they’re not so much concerned about six months’ improvement in survival and are much more concerned about their quality of life. So the issue with thalidomide was quality of life, whereas with revlimid, if you’re not having that impairment in quality of life, the improvement in survival is doubly beneficial, because you live longer and you feel good.

What about performance data, co-morbidities and so on? How much can you assess your patients to be suitable for IMiD maintenance therapy?

There are two components of that question. One is the induction component, which we didn’t allude to, but I think it’s very important because I think in the extreme elderly or the frail, you need to reduce the intensity of the treatment, to get more people to a stable phase where you can think about maintenance. But once you’ve got through that induction phase, if you’ve tolerated the drugs, if you’re well, then I think it would be suitable for the vast majority of patients, because in the absence of steroids, it’s very tolerable, and has very few side effects.

So, to sum up, what would you say are the messages coming out of your presentation on maintenance therapy in older patients with multiple myeloma?

I think the major take-home message is that the results of the clinical trials are starting to show that we are improving progression-free survival, and that this is turning into overall survival benefits; and the treatment is tolerable; and going forward, we need to consider maintenance strategies for people of all age groups, and especially in the elderly.

From what you were saying, lenalidomide is the front-runner, but there are other IMiDs on the way, too, aren’t there?

Absolutely, and I look forward to a stage where you can have a series of relapse-treatment-relapse options, that are based around a sequential use of different IMiD drugs, which have different characteristics.

Gareth Morgan, thank you very much for joining us on ecancer.tv.