High dose chemotherapy plus transplant remains standard care for young newly diagnosed multiple myeloma patients

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Published: 7 Dec 2015
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Dr Francesca Gay - University of Torino, Torino, Italy

Dr Gay talks to ecancertv at ASH 2015 about the long-term results of an open-label, phase III trial in which young (<65 years) patients with newly diagnosed multiple myeloma received standard treatment of high-dose chemotherapy plus autologous stem cell transplant (ASCT) or a triple combination of cyclophosphamide, lenalidomine and dexamethasone.

Results showed that the use of high-dose chemotherapy with ASCT remains the standard of care, producing higher progression-free survival (PFS) and overall survival (OS) than the cyclophosphamide, lenalidomine and dexamethasone combination. After a median of almost 4.5 years, respective PFS was 43 months versus 28.6 months and OS was 86% vs 73%.

The study also looked at whether using prednisone in combination with lenalidomine would be better then lenalidomide alone as maintenance

ASH 2015

High dose chemotherapy plus transplant remains standard care for young newly diagnosed multiple myeloma patients

Dr Francesca Gay - University of Torino, Torino, Italy


You were looking at some important issues in multiple myeloma and specifically newly diagnosed multiple myeloma in relatively young patients. What was it you were particularly wanting to look at?

We had basically two questions, the first one was the role of high dose chemotherapy and transplant in comparison with an oral triplet of cyclophosphamide, lenalidomide and dexamethasone, so transplant versus no transplant. And the second question of our trial was the maintenance strategy that we could administer, either the use of lenalidomide alone or lenalidomide plus prednisone.

And that was maintenance whether or not they had transplant or not?

Exactly. All the patients were first randomised to transplant and no transplant and after that all the patients after the consolidation, regardless of what they received, were again randomised to lenalidomide prednisone or lenalidomide alone.

Now, these were younger patients, what age group and how much of a genuine dilemma was it whether to give them transplants or medical therapy?

They were all younger than 65 years and they were all eligible for high dose chemotherapy. The objective of the trial was to see if transplant is required now that we have these novel agents, highly efficacious.

Sounds fascinating, what did you find?

We found that transplant is still the standard of care because transplant prolonged both the progression free and the overall survival. This advantage was noticed in all the subgroups of patients we analysed according to the age, the prognostic features and also according to the different maintenance treatments that we administered after this consolidation.

How big was that superiority?

It was really big because the difference in the median progression free survival was 43 months versus 28 months, so pretty much a high difference. The difference in the four year overall survival was 86% versus 73% with really a hazard ratio of 2.5 over no transplant versus transplant. So a really big difference.

Now, does that change practice, do you think?

I think it doesn’t change practice because the standard is the transplant but this confirms that transplant is still a standard, even with the use of novel agents. So the strategy now is to incorporate the novel agents into the transplant programme in the induction and in the maintenance after transplant.

Let’s get on to the question of prednisone or not. What did you do in that part of the study?

We randomised again all the patients that finished the consolidation to receive lenalidomide alone at the standard dose of 10mg or the same dose of lenalidomide plus 50mg every other day of prednisone. That was considered a therapeutic dose of prednisone. In both arms patients continued the treatment until progression of disease.

What did you find?

We found that prednisone was not well tolerated because about a third of patients had to reduce the dose very early with a median time of 4 months. And it did not increase significantly the progression free or the overall survival in comparison with the use of lenalidomide alone.

Where does this leave the use of prednisone in this setting?

Probably prednisone is not a drug that can be used in the long-term therapy. We can use the steroids in the induction, in the consolidation for a short time period to have a good cytoreduction but probably for the maintenance treatment where the toxicity is an important issue for patients the use of lenalidomide as single agent is well tolerated and, in the end, the addition of prednisone did not improve the survival.

And it’s nice to spare drugs.

Yes.

What, then, are the practical take-home messages coming out of your work from both of the parts of your study?

The first one is that transplant is the standard of care, even now that we have good novel agents and we had good results. So we have to incorporate the novel agents into a transplant strategy, both in the induction and in the maintenance. And that maintenance we know that prolonged remission and probably the use of the immunomodulatory agent alone, lenalidomide, is the right strategy because the prednisone adds toxicity without significantly improving the survival.