Therapy options and the future for multiple myeloma

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Published: 30 Mar 2011
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Prof Antonio Palumbo - University of Turin, Italy
Multiple myeloma is a disease found primarily in the elderly and the high proportion of patients over the age of 75 makes treating this disease very difficult. Prof Antonio Palumbo discusses the lack of clinical data to establish the optimal drug dose and schedule for elderly patients and talks about the need for better disease classification to help clinicians differentiate fit from less fit patients. Prof Palumbo outlines the different therapy options available for multiple myeloma patients, explains how clinicians decide between these and considers how the treatment of multiple myeloma will develop in the future.

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

Professor Antonio Palumbo (University of Turin, Italy)

Therapy options and the future for multiple myeloma now has the opportunity of talking with another of the experts here at the Rome meeting on Blood Cancer in the Elderly, one who has done a huge amount of work in multiple myeloma. Antonio Palumbo from Torino, why do you think this is such an important issue to talk about multiple myeloma in the elderly and have a conference entirely about elderly patients with blood cancer?

I would say there is a general issue because the baby-boomers that represent the vast majority of the age population that now are between the age of 50 and around 50, they will move and they become older and older. So our society will have a vast majority of subjects of the age of 65 or even more. So this is the general problem from an epidemiologic point of view.

In myeloma that is a disease of the elderly, there is today a dramatic change in the treatment and diagnosis of this disease because, generally speaking, we were before thinking about patients younger than 65 so defining younger patients and the elderly over the age of 65. Now epidemiology is changing and we are realising that under the age of 65 represents 30% of the disease; between 65 and 75 represents another 30% of the disease and more than 35% are over the age of 75. So we have one third of patients are so-called frail.

Basically today those patients are on the one hand under-treated, on the other hand over-treated. If you think that no specific trial has been so far run for patients over the age of 75 so we do not know the doses, we do not know the schedule of those treatments. So basically what is changing today is the awareness that we need to classify myeloma according to three different, specific groups and we do need to use the scheme we use for so-called fit: 65, 75 years of age patients and we need to change those doses in the more elderly, over the age of 75.

How, indeed, do you define the fit patient as compared with the frail patient?

We try to do it very easily, it’s not probably the most appropriate way but it is simple. We basically define the age, so the cut-off is 75 years of age from one side. On the other side we define if a given subject has a normal cardiac or pulmonary, renal or hepatic function. So if the major functions are normal, we classify the patient according to the so-called anagraphic age. If one of those comorbidities are present at that point, even a younger patient could be classified as a more older patient.

Could you explain, then, what is your normal approach to a fit patient who is older, as compared with a frail patient? What are the two different approaches you might use and which sorts of treatments?

It will be more complicated because today we have several drugs and several combinations so it would be a long story to explain it in detail. Generally speaking, what I would say is in the fit patient the full dose treatment that has been shown in the clinical trial, and is on the label of the drug, is the schedule we use. The so-called frail, over the age of 75, we usually use a 50% dose reduction from the label, from the trial that has been done until now.

So which combinations do you favour?

We have, let’s say, four types of combinations. One combination is alkylating agent plus an IMiD – lenalidomide or bortezomib. The other is corticosteroids plus, again, lenalidomide or bortezomib. We do favour the use of IMiDs more in the frail older patient; we do prefer the use of bortezomib in the younger one but generally speaking this could be one of the differences between the two groups.

So in a few words, what sorts of treatments do you recommend doctors to be considering for their older patients?

Certainly, in Europe at least, the standard is alkylating agent plus novel agents – bortezomib or IMiDs. This will be the standard of care, actually is what is considered the standard of care because it is the approved treatment for elderly patients in Europe, that is melphalan, prednisone and thalidomide or melphalan, prednisone and bortezomib. These are the two standards of care for elderly patients in Europe at least.

And how do doctors choose between thalidomide, lenalidomide and bortezomib, for example?

Bortezomib is an intravenous drug, it requires the admittance to hospital, although in an outpatient care, but it requires you to go to the hospital at least every week. So you certainly want to use this drug in more independent patients who might reach the hospital without major problems. You do prefer the oral administration in the more frail, less independent subjects.

Finally, what are the prospects then, in your opinion, for improving therapy for older patients with multiple myeloma?

Generally I would say one of the major prospects would be the use of continuous treatment. I would say I would consider two issues: one issue is a dose reduction in the frail patient; the other issue is a continuous treatment that allows to keep the disease under control for a longer period of time. So the future is based on those two issues: one, dose reduction to reduce toxicity and actually also discontinuation of treatment. On the other side, a continuous treatment until disease progression to prolong remission duration.

And what message would you urge doctors to take home from this meeting here in Rome?

The message is use properly novel agents and change doses and be aware that one third of our patients might require dose reductions.

Antonio Palumbo, thank you very much. Thank you for being on

Thank you very much for inviting me.