Main issues in treating elderly patients with myeloma

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Published: 1 Apr 2011
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Prof Jesús San Miguel - University Hospital of Salamanca, Spain
Prof San Miguel interviewed at ecancer’s Blood Cancer in the Elderly European Expert Forum: Myeloma, a disease with a median age of around 65 years, is now being tackled with a new generation of drugs with lower toxicity profile, eg pomalidomide (a derivative of thalidomide) and carfilzomib. Also discussed are the issues of a lack of geriatric clinical trials, transplantation in the elderly and tolerability.

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

Professor Jesús San Miguel - University Hospital of Salamanca, Spain

Main issues in treating elderly patients with myeloma

Hello, and welcome to ecancer.tv. I am delighted to welcome Professor San Miguel; you are co-chairing a very important session today on impact of age and comorbidities in multiple myeloma. What are the main issues in terms of treating the elderly in myeloma?

I think myeloma is an interesting disease because it remains an incurable disease and it’s a disease of the elderly population; the median age of myeloma patients is around 65 years. Different from other B cell malignancies, such as CLL, in which usually because the life expectancy was much better than in myeloma they were rather conservative in the treatment of the elderly population. The myeloma community, as soon as we get some new drugs we think that these drugs could be of value, not only for the transplant candidate, the young myeloma patients but also for the elderly. This probably explains why, in the recent trials conducted in the elderly population, the median PFS is around 36 months and this figure was the overall survival in the area of melphalan/prednisone for elderly myeloma patients.

Besides this it is also important to mention that in the elderly population you have a problem and the problem is the comorbidities. These also impact on the decision of what treatment do we use in the elderly patients.

Obviously myeloma is a very active field in terms of novel therapies, lots of very exciting new therapies coming through. Presumably one of the issues is toxicity, particularly in relation to the elderly? Are there novel agents coming through which you think have a better safety profile?

Yes, definitely. Let me point out two issues: first of all, we are learning. This has been a painful learning process but eventually we have learnt how to manage the toxicity of the all new drugs, because some of the drugs, such as thalidomide, bortezomib, lenalidomide is still a new drug, but this too. We know now better how to handle them about some of the side-effects that they produce. Nevertheless, we are now having a second generation of drugs that could be even more active and with a lower toxicity profile.

If you talk about IMiDs, don’t forget that we started with thalidomide, a very old drug that was discovered eventually that it was a valuable drug for angiogenesis and cancer. Then comes the second generation – lenalidomide; now we have the third generation just knocking at the door and this is pomalidomide, that has proved to be very effective, even in patients that are refractory to thalidomide or lenalidomide. If you move into the proteasome inhibitors, the same scenario – you have, until now, bortezomib but now we have carfilzomib, a second generation, and a third generation is already being cooking. Now we have not only these type of drugs, we also have histone deacetylase inhibitors, we have now new monoclonal antibodies. In other words the expectancies for the myeloma community are becoming much better; it’s not only a reality it’s also a promise.

It’s interesting. You mentioned earlier about other malignancies, CLL typically a median age now of about 72 and yet we’ve also heard at this meeting that 70% of patients are not actually eligible to go on clinical trials. That’s less of an issue in myeloma?

Yes, probably because, as I mentioned before, the life expectancy in CLL without treatment is better than in multiple myeloma. If you are able to survive for four or five years without treatment, particularly because you are in earlier stage CLL, then treatment is not a major issue. By contrast, in myeloma usually most of the patients are diagnosed at stage 2 and 3 and at that time they are symptomatic and they need some type of treatment.

Worth, perhaps, just touching on the role of transplantation in the elderly, is there a cut off period?

Transplantation initially was recommended until the age of 70; now the cut off is 65 and there is a window between 65 and 70 and even 72 or 73 because there are some patients that are really fit and can tolerate very well the high dose melphalan. In fact, I would say we talk about transplantation, but it is not an appropriate term. Transplantation is something different from you that is even by another person to you. This is the allogeneic transplantation. The autologous transplant is not a transplant, it’s just to take out your stem cells to keep frozen, to give you high dose chemotherapy and to rescue the toxicity of the high dose chemotherapy with your own cells. I would call it intensification more than transplantation.

So obviously we’ve just talked about novel therapies, one of the main aims is looking at efficacy of these drugs but also the tolerability. In other words, the future in myeloma is pretty bright in respect to treating the elderly patients?

Nevertheless I should say that probably, with some of the novel agents, the ones that are still in clinical trials, probably we will need to learn a bit more about the toxicity, mainly because some of them show little efficacy as single agents different from what we have experience with thalidomide, lenalidomide or bortezomib that as single agents were highly efficient. Some of the new agents had little efficacy as single agents but they could be very important in combination and when you move into the combination, the toxicity can duplicate or there can be synergies, not only in efficacy but also in toxicity. This will be again a learning process that we should do carefully and always think to the quality of life of the patients.

That’s a very good point. Professor San Miguel, thank you very much.

A pleasure.