Lenalidomide with melphalan + prednisone and lenalidomide maintenance for multiple myeloma

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Published: 13 Dec 2011
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Prof Antonio Palumbo - University of Torino, Italy

Prof Gareth Morgan discusses the updated results for elderly myeloma patients enrolled in the MM0-15 trial with principal investigator Prof Palumbo. The study invloves an IMiDs immunomodulatory agent, Lenalidomine, which has a dual mechanism of action: its tumouricidal effect directly leads to tumour cell death, and its immunomodulatory effect may keep the tumour in remission. The structure of the trial is; phase 3, randomized, placebo (Pbo)-controlled trial, MM-015 compares MPR-R with fixed-duration MPR and MP induction in transplant-ineligible NDMM pts. Interim results showed unprecedented reduction in disease progression risk with MPR-R (Palumbo et al, IMW 2011); this analysis focuses on pts aged 65-75 yrs in whom the greatest benefit was observed.

 

Abstract 475 can be accessed on the ASH website here.

 

This programme was made possible with an educational grant provided by CELGENE.

2011 ASH Annual Meeting, December 10-13, San Diego, USA


Lenalidomide with melphalan and prednisone and lenalidomide maintenance for newly diagnosed multiple myeloma

 

Professor Antonio Palumbo – University of Torino, Italy

 

Hello, my name is Gareth Morgan, I’m Professor of Haematology at the Royal Marsden Hospital in London, England. I’m here today at the 53rd Annual Meeting of the American Society of Haematology with my good friend and colleague, Professor Antonio Palumbo from the University of Torino. We’ve heard some exciting data in this meeting and we’re going to talk now about the 0015 study in which Antonio has been a principal investigator. So, Antonio, would you like to describe the study for us?

Thank you very much for the invitation. Yes, I think this is a very important study because for the first time it’s using the usual induction regimen with melphalan plus lenalidomide but this time followed by continuous treatment with lenalidomide until progression. Basically what is coming out from this study is that with the use of the maintenance approach we increased the progression free survival over a median of ten months. So where we were before around 20-25, we are now moving to 30-35.

So, what you’re saying is that MPR plus R maintenance looks like a new standard of treatment?

I think this will change, certainly, the treatment paradigm in elderly patients, not only for lenalidomide but also for other drugs. The introduction of a maintenance approach will be very, very important and will make a significant improvement, at least in terms of remission duration. We still need a longer follow-up to see the impact on overall survival but certainly in terms of remission duration it’s adding around 30% longer remission duration when used as a maintenance approach.

But what you have here, I think, is an update, a re-analysis with longer follow-up. And this is a three arm study in fact and perhaps you could describe what’s happening to the middle arm of the study, because I think that’s really exciting as well.

Well the study is a three arm study, as you said: MPR followed by lenalidomide maintenance versus MPR alone versus MP. MPR followed by lenalidomide maintenance is always superior to the other two arms. MPR alone is superior to MP only in patients between 65 and 75 years of age. This is telling us a general story and the story is that in the frail elderly, over the age of 75, we do need some important dose reduction because the dose intensity we deliver to a patient of 65 cannot be the same we deliver to a patient of 80 years of age. If we do not make any dose reduction, the risk of discontinuation is very high and from this point of view the risk of losing efficacy.

But in this 65-75 age group it looks MPR-R best, MPR not so good but better than MP? And that’s for PFS?

This is for PFS, for overall survival. We are starting to see an improvement in overall survival for patients 65-75, we do not see an improvement for overall survival for the old population, but I will say that probably here a longer follow-up is needed.

I just wanted to be clear, so in the 65-75 age group you’re starting to see a survival benefit for MPR-R, what about for MPR alone versus MP?

No, actually in this age subgroup the survival benefit is mainly seen in MPR followed by R. MPR alone or MP are having the same outcome.

So one of the conclusions would be that we’re starting to see really clinically significant benefit for people treated with maintenance and that maintenance is now a real concept in patients with myeloma?

I would say, generally speaking, maintenance is a general concept for patients with myeloma in all age groups – younger and older than 75. We are starting to see a survival advantage for patients in the group 65-75 using a maintenance approach.

But you’ve always been a big exponent of being very careful with the extreme elderly and I think it’s an approach we all buy into as well.

Certainly we have to change our practice and be more gentle with the elderly, with the frail, in order to avoid too many unacceptable toxicities.

OK, well thank you very much Antonio, it’s been a pleasure talking to you today. And thanks for going through that with us.