Treatment of elderly MDS patients

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Published: 4 Apr 2011
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Prof Antonello Pinto - National Cancer Institute, Naples, Italy
Myelodysplastic syndrome (MDS) is a disease that is typically occurs in elderly people. Traditionally this has been a very difficult disease to treat but more recently a number of active agents have become available which benefit patient survival. Prof Antonello Pinto discusses MDS treatment, explains the importance of MDS drugs being taken over a long period of time, speaks about the role of haemograms in monitoring patient condition and outlines how patient response is defined. Prof Pinto explains the importance of good communication not only with the patient but also with the family. A supportive family or patient advocacy group can be a valuable way to help remind elderly patients to take their medication, to collect data for the clinician or clinical trial or to help ensure that drugs are accessible to the patient in easily manageable packaging.

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

Professor Antonello Pinto (National Cancer Institute, Naples, Italy)

Treatment of elderly MDS patients

ecancer television is here with the Blood Cancer Conference, Blood Cancers in the Elderly, here in Rome. Antonello Pinto, you’ve just been chairing a session on advocacy but before that I want to ask you about your own subject, MDS. MDS is a disease of old age, what do you consider are emerging as the changes in therapy or changes in approaches to MDS, especially considering that populations are in fact getting older and this disease is more significant?

Myelodysplastic syndrome is a disease typically occurring in aged people because the median age at incidence is around 72-75 years, so it’s the kind of situation which typically applies to the elderly. A few years ago no active treatments were available and so there was really a problem and most of those patients were either treated with intensive chemotherapy, like AML patients, but not a great number of those patients were able to stand this very intensive treatment, or these patients were offered supportive therapy and that’s it. Now the scenario has changed because a number of very active agents are available. For example, the typical example of these is the use of DNA hypomethylating agents which, being able to modify the gene expression profile of tumour cells, are able first to resolve the cytopenia so to improve the bone marrow function, even without clearing off the tumour cells from the marrow like one would expect in acute leukaemia. Then, by improving the cytopenia, these agents were shown to be able as well to improve the overall survival.

Do you consider, then, that because of these therapies and the fact that patients are responding even when they’re older, that there are now new ways of treating older people?

Yes, that’s true. One of the problems we have with these agents is that we need to keep on the patients’ treatment as long as possible because the effects are late. The beneficial effects do come very late in the treatment so it’s important to continue and it’s important to have the support of the family and of the patient to accept a prolonged treatment.

And what sort of criteria do you look for for response because you may not get a complete response?

This is a very critical point because up to a few years ago, even in treating MDS like in acute myeloid leukaemia, the idea was to evaluate as effective a treatment that was able to completely clear off the marrow from tumour cells and to restore the normal marrow appearance. Emerging data clearly showed that if one treats patients with agents such as DNA hypomethylating agents, you don’t probably need to have the complete remission picture in the marrow to improve survival of these patients. So even a partial response and even an improvement in the haemogram, a significant improvement in the haemogram, translates into an improved survival which was something going against the typical dogma of acute myeloid leukaemia. So it has been really impressive news.

So in everyday practice, how do you advise a clinician to approach this? What exactly should he or she do?

Communication, and this is an important issue, with the patient should address specifically the fact that you obtain the clinical benefit, with these kinds of diseases time is needed. So patient expectation should comply to the idea that they will see the results over a longer time.

So you ask the patient what’s happening?

Yes, and actually it’s the reverse. The patient usually has to ask what do you think is going to happen? And what we usually do with this patient is to make clear that our primary endpoint is to restore the marrow function. We usually tell the patient that the aim of this treatment is to have your marrow to work as it was before and it takes time.

Now if you’re not getting a complete response, what sort of tests can you make and how do you manage the disease, to keep it a low level?

One problem we have that it is difficult to ask an aged individual to repeat a number of bone marrow biopsies which are disturbing, not painful actually, but surely disturbing. So we can rely on the haemogram and so it’s important to us and the patient to follow quite strictly the haemogram prescriptions because through there both the physician and the patient may realise how the blood levels are changing, because the target is to improve the blood cell levels independently from the fact that the marrow changes or not. This is a little bit of a different view.

So there are some measurements but also you need to keep a look out clinically for what’s happening?

Yes, of course.

And then do what?

After a first evaluation we try to delay a little bit the clinical checkouts because we don’t want all these patients to come in and out from the clinic. It will also depend on the age, so a good way would be to advise the patient to send us the results of the blood tests and if there are no clinical problems we can try to be a little bit more intense in controls and checkout.

So you could adjust the dose?

Yes, we can adjust the dose.

Now interestingly enough there’s a bit of a lack of data in myelodysplastic syndrome, simply because it affects older patients and older patients traditionally have not been in randomised trials. Now one of the reasons rather overlaps with the session that you’ve just come out of on patient advocacy, and that’s about compliance. I think there was a prejudice against older patients, simply because they often don’t comply and so the doctors don’t know what’s happening.

We have two issues here. The first one is that, as you said, there is the tendency not to include aged patients in clinical trials. This is for several reasons, this is not a recent issue, it’s from years that investigators would actually work into clinical trials, try to force their colleagues to accrue the patients into those trials. In the patient advocacy session we have been discussing this issue and unfortunately still there is the tendency from many physicians not to consider an aged patient for a clinical trial, even though the eligibility criteria would allow this inclusion, simply because of misconceptions about this. This creates a discrimination.

But another problem is that treatments may be protracted, especially in the case of diseases like MDS.

That’s true and the problem is that the more modern treatments, which are mainly targeted at changing the biology of the disease, do need prolonged time of administration. Most of those therapies can be given as tablets or sub-cue injections and you need the patient to continue treatment for months. So a problem comes out with the elderly people. A good idea would be to try to put the family into the system because we sometimes really need the help of the family to remind the patient to take his tablets every day. One of the problems emerging from data analysis is that elderly patients tend to be less adherent to protocol administration of drugs. That’s because they may sometimes forget and so if you find out a supportive family environment, this will be very important to ensure that they take all the medication.

So you’ve got a supportive family and you can have patient advocacy groups, lots of methods and even tricks and technology ways of remembering to take your medicine. You have to wait a long time for your data in some of these diseases though, so do you have a solution for that? Perhaps involve the community or the family to track the data so that we do get hard information?

This would be a very interesting idea, trying to keep the family system and the patient into data collection and evaluation would be a good idea in the sense that many of the clinical parameters that differ from physical evaluation, of course, can be achieved by local labs and so on. So having the family to be part of the data collecting system could be a way to avoid those problems. Another very important point, which seems apparently a trivial point but is critical, for example, that many of the ways in which the tablets and the medication are presented to the patient can be troublesome for an older patient. Opening a blister of tablets is very easy for a young patient but can be complicated for an old patient. So also the way of packaging medications could be a good way to improve treatment adherence among elderly individuals.

Could I get you to sum up what, for you, is coming out of this conference? It’s first and foremost about myelodysplastic syndrome, you’ve mentioned about compliance now, but what practical points are you taking home from this conference on blood cancer in the elderly that you would pass on to busy doctors?

The most relevant information is that now we have tools to significantly improve survival of older people and life expectancy in elderly people nowadays with the myelodysplacia, but I have to say with several other types of tumour, is no longer dependent by the disease itself but it depends strictly on how the disease is treated. If you approach correctly the management of the disease, they you can save in survival times and you can prolong the life of those patients.

And would you say to doctors that enough new treatments, emerging treatments are coming forward, not only for MDS but some of the other hematologic malignancies.

Yes, myeloma, for example CLL is another example and so on. So I think that we should no longer consider that an elderly patient, because of a blood cell cancer tumour, should necessarily have his life expectancy reduced because of the tumour. So we should try to provide him with active treatment.

It’s great to have you with us, Antonello. Thank you for being here on

Thank you very much.