Progress in myeloma survival rates

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Published: 25 Jun 2010
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Professor Jesús San-Miguel - University Hospital of Salamanca, Spain
Prof Jesús San-Miguel, speaking to Prof Gordon McVie, talks about the progression in myeloma survival rates and the contributing factors. Data from a large randomised trial is showing that zoledronic acid compared to oral clodronate is superior in preventing skeletal complications and is associated with prolongation of survival.

This interview is supported by an unrestricted educational grant from Novartis Oncology.

Click here to see Prof Jesus San-Miguel speaking to ecancertv at ASH 2009.

15th Congress of the European Hematology Association (EHA), 10—13 June, 2010, Barcelona

Interview with Professor Jesús San-Miguel (University Hospital of Salamanca, Spain)

Progress in myeloma survival rates

Professor San-Miguel, welcome to ecancer.tv, thank you for fitting us in to your very tight schedule here at the EHA meeting in Barcelona. Tell us a little bit where you’re from?

OK, I’m from Spain, I’m from Salamanca, the University of Salamanca, one of the four oldest universities in the world. It’s a small city but everything goes around that university.

And you know a lot about malignant multiple myeloma? You’re a myeloma expert.

I have been working in myeloma since 1977, I think it’s a long way. And probably this explains why we have done some contribution to the field, nothing special but…

I was at ASCO three days ago and I got my little badge for being a member for 35 years, so that takes me back in time too. In my day it was melphalan prednisone but there was a nice phase III paper on zoledronic acid up front.

OK yes, the UK group led by Gareth Morgan presented very interesting data and these data, together with other new data from the same group, will also be presented here at EHA at a Presidential Symposium. And the data shows that zoledronic acid, this is a large randomised trial, as compared to oral clodronate, is significantly superior in prevention of a skeletal complication and on top of that, something that is new and is really intriguing and is really attractive, also it’s associated with a prolongation in survival.

That’s the surprise and it’s popped up also in breast and there are hints that it might be coming down the line in prostate, but in multiple myeloma you start usually with a bony presentation many times. The question is, is this going to go quickly into front line? Is this near to being best practice?

No, but we are using zoledronic acid in all patients with symptomatic myeloma, with bone disease. That is something very common in multiple myeloma. We use, up front, zoledronic acid. What has not been done is what is reported in this trial – an appropriate comparison through a randomised comparison in order to show if the benefit not only applies to the bone disease but also to the survival. How this can be explained is another question. One possibility is, yes, that by reducing the bone complication, the skeletal event complication, the patient is more fit and this can contribute to the prolongation of the survival. The other hypothesis is that the bisphosphonate can have, at the same time, an anti-tumour anti-myeloma effect. These need to be clarified.

Through the exercise of the matrix is one of the theories that I’ve heard and you think this is a possibility. So that was ASCO, now we’re in Barcelona, European Haematology Association and there’s some really nice data coming up on some new agents. Would you like to tell us about them? You’re involved, and the Salamanca Group, and you have several abstracts, ten I think from your group?

Yes. I think this is the good news for myeloma. Unfortunately myeloma continues to be an incurable disease and it’s not yet a chronic disease but we have made tremendous progress in the survival of myeloma patients, first by using three drugs – thalidomide, bortezomib and lenalidomide in relapse or refractory patients. And these lead to the prolongation in the survival of around one year. Then these three drugs have been moved to the up-front setting and again we have gained for the patient prolongation in survival also of approximately at least one year. The good news is that when the patient relapses, now they have new options – we have the histone deacetylase inhibitors that as single agents are not very efficient but in combination with bortezomib, proteasome inhibitors, with IMiDs and lenalidomide have a synergistic effect. Both vorinostat and panobinostat have been shown to be effective in patients that are previously refractory to bortezomib, for instance.

And these HDAC inhibitors are attacking the epigenetic areas, are they?

Yes.

So it’s a totally different advance. In the beginning they have been quite disappointing, particularly in solid tumours which is more of my field, because it’s single agents but as usual the haemato-oncologists are ahead of the game and you’ve got them in combination.

Yes, but the rationale for using combination is not empirical, the rationale is based on the mechanism of action. And if you put together a HDAC-6 inhibitor with a proteasome inhibitor we reinforce the way that you can kill the cells and you can block the proliferation and you can induce the apoptosis. But this is not the only new drug, we also have elotuzumab, we have a new monoclonal antibody that, in combination with lenalidomide, is showing excellent results, elotuzumab – anti-CS1. We also have proteasome inhibitors – carfilzomib is showing clear efficacy in myeloma, similar to bortezomib but with the important advantage that the incidence of peripheral neuropathy is very low. We also have new IMiDs: pomalidomide is a third generation IMiD and another good news. In patients refractory to lenalidomide, 40% of these patients can respond to pomalidomide. And we also have an old new drug, bendamustine, a drug that was generated in Eastern Germany and now this drug is showing high efficacy in relapse refractory patients, particularly also in combination because the drug was tested as a single agent with 50% response rate – a very high response rate. But in combination with thalidomide, for instance, and prednisol, the response rate in relapse refractory patients is approximately 70%.

So this is still multiple myeloma?

This is multiple myeloma.

Because, of course, at ASCO there was the big study presented, the randomised trial of bendamustine and rituximab versus CHOP rituximab and it looks to be superior. Certainly I interviewed Bruce Chisholm on ecancer.tv and he was extremely excited. He didn’t mention the multiple myeloma data.

But the multiple myeloma data is really encouraging.

So we’ve got the astalase inhibitors, we’ve got the second and third generation proteasome inhibitors and we’ve got efficacy…

Third generation IMiDs. The bendamustine.

Bendamustine, which was 1960s I think it was, when I was at medical school.

You are right, and these are not the only drugs, there are several ones that we are also testing in phase I, some of them are also promising but we need to wait a bit more.

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