14th International Myeloma Workshop

Hot topics at IMW 2013

Dr Mohamad Mohty – Nantes University Hospital, France

I’m Mohamad Mohty, I’m Professor of Haematology at the University Pierre et Marie Curie in Paris. I’m also Head of the Haematology Department at the Saint-Antoine Hospital there and we’re here today at the International Myeloma Workshop in Kyoto having some good time, good weather, exciting and very challenging time for myeloma treatment and understanding.

What data has been presented regarding surrogate markers and new imaging techniques in MM?

I think this meeting is quite an interesting one because it provides a nice balance between educational sessions for the general audience but also giving some time to discuss some hot issues and indeed, as you mentioned, the impact of minimal residual disease. This is something which is really on the cutting edge in recent years and that’s quite funny because in the haematology community minimal residual disease has been always considered as a very important surrogate marker for survival in any disease. In acute leukaemia we know this, in CML, except in myeloma until recently. I think one of the explanations is that the old drugs, standard chemotherapy, did not allow to achieve any significant or high response rate, namely complete remission. Now with the advent of all the novel agents, we are seeing some very important and significant CR rates. So definitely the question of minimal residual disease is coming on the stage because, of course, one would like to see what is the true impact of any given combination for an individual patient. 

So it’s quite tricky because the tools to evaluate minimal residual disease are currently debated. Of course flow cytometry is becoming more and more popular and there is quite a nice body of evidence suggesting that this is a reliable tool, reproducible, can be almost done in more than 90% of cases and there is data from different groups highlighting a clear correlation between achieving negative minimal residual disease and improved survival, progression free survival but also data suggesting overall survival.

In addition to evaluating minimal residual disease with flow cytometry, I think we have seen, during this meeting, some important communications about the rule of new imaging techniques that, in my opinion, can be used in addition to minimal residual disease to further refine the response level. Here we’re speaking about MRI but also PET scan but also within the PET scan techniques different techniques are being developed. I think we’re not yet mature enough because these techniques are not yet standardised between centres; we’re not mature enough to use them as part of the treatment strategy. Definitely within a clinical trial this is OK and the data is now being released progressively but also this is not yet mature, we are definitely on the right track.

What is the latest data regarding the use of monoclonal antibodies?

Again, a very exciting time because, as you know, for many years we’ve been lacking monoclonal antibodies in the field of myeloma and in the last three or four years we’ve seen some signals. One of the monoclonal antibodies is elotuzumab, which is directed against the CS1 protein, and elotuzumab alone, unfortunately, is not an active monoclonal antibody. However, when used with other novel agents, namely lenalidomide, for example, but I think it may prove true also with bortezomib, it is showing some nice efficacy, at least in relapsed myeloma. But probably the most promising and most exciting monoclonal antibody is indeed daratumumab which is now coming into the field quite rapidly, I think, and that’s good news for the community but also, I think, for the patient because this is directed against C38. This is a key molecule for plasma cells and we have been really very pleased, and this has been also communicated during this meeting, to see that even as a single agent which is quite unique because until recently most of these novel agents that are being tested proved to be little efficient when used as a single agent. However, daratumumab used as a single agent has definitely a dramatic efficacy with a very favourable, at least from the available data, safety profile. So I think the near future will bring us some good news about this molecule which may become, who knows, the rituximab of myeloma.

Can you tell us more about the current debate regarding whether to use autologous stem cell transplantation or not as a first line therapy?

The use of auto-transplant frontline versus delayed auto-transplant is something that is now coming again into the scene. As all of us know, until recently autologous stem cell transplantation was considered as the standard of care in those young myeloma patients without comorbidities, usually up to the age of 65. And this has been validated through randomised phase III trials from different groups, however, the increasing use of the novel agents and the highly significant level of response rate that can be achieved with these novel agents is currently challenging the use of auto-transplant frontline. So one of the debates, and it was quite a nice debate, I must confess, during this meeting was the debate should we go to frontline auto or should we go to delayed auto. That was quite funny because you have a European perspective which goes in general in favour of frontline auto whereas you have a North American perspective rather favouring the delayed auto. My personal opinion, not just as a European, but I think the available research evidence, and I think we really need to rely on evidence-based data, is still in favour of proposing auto-transplant as frontline and this should not be delayed except in some special few cases.

So definitely the question, in my opinion, is not auto versus novel agent but rather how to take advantage of both auto and all the novel agents. And this is exactly the idea behind this important concept of providing a triplet induction with novel agent followed by a conditioning and high dose therapy and autologous stem cell transplant but also giving a consolidation short-term and, for a few selected patients, probably maintenance therapy. In my opinion this full treatment package is likely today the one that can allow the patient to achieve the longest progression free survival. Of course the final answer to the question of auto frontline versus delayed auto will come from the two on-going large randomised trials, the one from IFM, the 2009 DFCI but also the trial from the European Myeloma Network. But until we’ve got the final results of these two trials, I think auto should remain the standard of care for the young myeloma patient.

How could carfilzomib and pomalidomide influence therapy choices in the future?

You’re raising the question of the potential role and benefit of the novel, very recent, agents that were approved and when it comes to proteasome inhibitors we’re speaking here about carfilzomib. Interesting data, definitely. I think, however, the data is still limited. I think very interesting but the first generation, the so-called first generation proteasome inhibitors still have some good time and they are here to stay. We need to learn more about these novel proteasome inhibitors and we are all aware that there are on-going clinical trials. When it comes to IMiDs, indeed pomalidomide is the novel and quite great key player because this drug proved to be efficient in those patients who are refractory to proteasome inhibitors but also to lenalidomide. This is not only an advantage, a significant benefit, in terms of progression free survival but also overall survival. So pomalidomide is providing now something of great value to many of these patients who otherwise their outcome is rather very dismal.

Do you see MM become a chronic disease in our lifetime?

You’re asking absolutely all the hottest and challenging questions in the field of myeloma. I’m not sure I have the right answer to this. So it’s a philosophy – how do you view myeloma? Is it a curable disease or is it a chronic disease? My personal feeling is that it’s not black and white and the truth is something in-between. In a great number of patients actually the focus will be to bring it into a chronic disease and more and more we are closer to this call. However, I don’t feel that we should completely eliminate the idea that we will be able to cure, or at least to achieve a functional cure, in a small proportion of myeloma patients. We know from historical data that there is a small fraction of myeloma patients who can achieve long-term disease-free survival. So we probably need, and lots of work is on-going on trying to dissect the different myeloma. Because we’re speaking about myeloma but this is not a single disease, this is a huge number of heterogeneous diseases and one would like to identify quickly this small group of myeloma patients who are likely to achieve long-term disease control and this is what I would personally call a functional cure. So it’s not chronic against cure, it’s probably both of them depending on the type of myeloma and I think this is really a wonderful time for the understanding and for dissecting the very deep path of physiology of this disease.