Autologous stem cell transplants for multiple myeloma

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Published: 4 Apr 2011
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Prof Fernando da Costa - UTM, Instituto Portugues De Oncologia, Lisbon, Portugal
Traditionally multiple myeloma patients over the age of 65 have been considered unsuitable for autologous stem cell transplants, however, some centres will treat patients up to the age of 75. Prof Fernando da Costa argues that patients over 65 should considered for transplant if clinicians have followed strict selection criteria. Patients are normally conditioned with melphalan before receiving a transplant but many older patients can not tolerate a full dose and clinicians must decide between giving a reduced dose or not offering the transplant. Prof da Costa explains why he does not believe reduced intensity conditioning is suitable for elderly patients, stresses the need for more randomised clinical trials to establish the optimal doses of conditioning drugs and summarises how to determine if a patient over the age of 65 should receive an autologous stem cell transplant.

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

Professor Fernando da Costa (UTM, Instituto Portugues De Oncologia, Lisbon, Portugal)

Autologous stem cell transplants for multiple myeloma

ecancer television has not heard very much about bone marrow transplantation, or stem cell transplantation, here at the meeting of Blood Cancer in the Elderly but now I’m going to hear from you, Dr Fernando da Costa from Lisbon, because you’ve been doing auto transplants for quite a long time and although older patients may well be excluded, older patients with multiple  myeloma, because you’ve just come out of this wonderful session on multiple myeloma here in Rome, the older patients can be excluded but apparently that might not necessarily always be the right thing to do.

Well we do have a cut-off problem there. Traditionally we do not transplant patients over the age of 65, but between the age of 65 and, in some centres, higher than 70, up to the age of 75.

So there has been a chronological cut-off that has been applied?

Yes, there has been a chronological cut-off but probably the chronological cut-off per se is not the wisest one to use.

So what do you think now that you’ve been hearing all the comments here?

I think that after the age of 65 one should be more careful applying the rules of selection of patients as we normally do with other diseases including amyloidosis which is something that comes up with multiple myeloma sometimes as a complication. So there might be still a place for Melphalan intensification in people older than 65 at least up to the age of 70, or even 75 in some centres, according to very strict selection criteria. The problem with giving  high doses in older patients is that the optimal dose of Melphalan is 200mg/m2 and most of the people older than 65 normally only tolerate doses up to the dose of 140mg/m2. So the question remains if it is still worthwhile to give a lesser dose of Melphalan but still not abandoning it for people that are older than 65 or something like that.

Now indeed you have got some new methods, you’re using mini transplants or reduced intensity conditioning. Does that solve the problem?

Above the age of 65, probably not. However, we do have results on reduced intensity conditioning for people older with, for instance, acute leukaemia or myelodysplasia. We do know that, although the conditioning has been reduced and so the immediate mortality has been reduced, that is the procedure related mortality , we do have a problem with harnessing graft versus host disease in these people. We do know that there is a tendency for more severe graft versus host disease with older patients. So in multiple myeloma I would say that reduced intensity conditioning, it’s probably a far off option for people who are really old.

Could you tell me, then, what you have been able to do, what your ideas are and what data we do have about auto transplants in older patients with multiple myeloma?

There are several theories that have been published showing that you can actually give the highest dose to people with multiple myeloma. The general impression is that when you compare people that, for instance, received only 100mg/m2 and you compare them to, for instance, treatment with MPT, as the French have done, there was no benefit at all. So if you want to do high dose Melphalan, you really have to be sure that the patient will benefit from the highest dose. If you have a fit enough patient then, still at this time because we do not yet know if the new drugs will eventually replace high dose treatment, I would think that the best option, once you have a very fit patient, even if it is between 65 and 70, will be to start treatment envisaging the possibility of doing Melphalan high dose as consolidation. But there are randomised trials comparing the effect of high dose Melphalan, if it is still needed or not in the age of new drugs, mainly when you use Bortezomib and Revlimib as induction treatment.

So there’s a need for randomised controlled clinical trials to establish the data, but you do have some preliminary data already from your work?

Not from my work itself, but we do have the impression that in people that are above 65 probably if we consider the possibility of going on treating them with some form of maintenance, maybe Melphalan high dose may not be necessary. Then again, I have to confess that I have a bias, I’ve been transplanting all my life and I believe that it has not yet been proven that Melphalan high dose is not necessary for people that can actually go with the treatment, can actually endure the treatment.

Well, busy doctors who are facing up to the decision about what to do with their patient, what would be your advice to them, then? Can they consider auto-transplant?

I think so. I think that if you have a patient who is between 65 and 70, or maybe some older patients, if they are fit enough, if they have the will to go through the treatment of Melphalan high dose, I think it is an option to consider up front and in that case one should devise a treatment not using Melphalan low dose up front and doing it as consolidation. But then again, this is something that you must discuss with your patients but certainly there is still room for high dose consolidation in very fit patients, even above the age of 65.

And finally and very briefly, I can’t resist asking you for you impressions of this meeting, this session, on multiple myeloma. Are you optimistic now that you’ve heard about all of the different therapies?

Yes, I’ve always been optimistic. I think that this was a very timely meeting considering the importance of the elderly population. I have certainly a message of hope for all of those treating myeloma. When I started treating myeloma, twenty-something years ago, we had people that probably would not survive more than 18-24 months. Now we have been having patients who have been alive for more than ten years and probably the trend is to go on improving, prolonging life and above all we’ve been improving a lot of the quality of life of these patients which is absolutely the most important fact in modern day medicine.

Fernando da Costa, thank you very much for joining us on ecancer television.

Thank you, my pleasure.