14th International Myeloma Workshop
Multiple myeloma: transplant setting in the younger patient
PM: Professor Philippe Moreau – Centre Hospitalier Universitaire de Nantes, France
PS: Professor Pieter Sonneveld – University Hospital Rotterdam, Netherlands
HG: Professor Hartmut Goldschmidt - Universität Heidelberg, University Hospital of Internal Medicine, Germany
PM: Welcome back to Kyoto for day two of this myeloma workshop. We had today a lot of discussions regarding the role of autologous stem cell transplantation as part of frontline treatment of young patients. We discussed about the induction regimen; we discussed about the role of consolidation of maintenance and of the role of transplantation itself in the setting of novel agents. So today I’m joined by two leaders in the field, from Germany Dr Goldschmidt and from the Netherlands Pieter Sonneveld. I would like to ask you the first question regarding the best induction regimen so, Hartmut, what is your opinion regarding the best induction prior to autologous stem cell transplantation?
HG: We use this approach also in patients with first relapse and if patients have information from the internet from patient support groups that this is a very attractive approach then we say, “OK, it’s your decision and we would treat you outside of a clinical trial.” We have around ten patients per year that we treat outside of a trial because the patient is very motivated, gets some information that is helpful and then we say, “OK, we will do it.”
PM: Good, and what about your opinion, Pieter, regarding the role of allo-stem cell transplantation in the Netherlands?
PS: We have been disappointed in the effect of allogeneic transplant in first line treatment especially. This experience comes from a cumulative analysis of several trials where there was the option of allogeneic transplant for patients that had an identical donor. In the end it came out that allo was not better than other therapies in those patients. So we decided that for first line treatment we would only do that in the context of a clinical trial and in fact we have such a trial where we give bortezomib and lenalidomide after the allogeneic transplant with the purpose of manipulating the graft. So outside clinical trials we are not accepting patients for allogeneic transplant; we are accepting patients for allogeneic transplant in first relapse if they are young, good condition and have poor prognostic characteristics like poor FSH or otherwise.
PM: So we discussed previously with Hartmut regarding the role of autologous stem cell transplantation, and do you think that we need to apply systematically outside clinical trials high dose treatment as part of frontline treatment in young patients? What is your opinion? Because, again, a hot topic, big debate, should we, should we not?
PS: Yes, I understand your question. The answer is yes, for now and probably for the next couple of years because we are running a trial, like the French are also running a trial, where we compare high dose therapy with standard dose therapy plus novel agent. In our case that’s melphalan, standard dose melphalan, and as long as we do not know the outcome of the trial, high dose melphalan plus autologous transplant remains the standard for all patients.
PM: That’s good. So we discussed also about the role of the best induction treatment, triplet induction, I think that there is a consensus for triplet induction, then high dose. Then what about the role of consolidation? Hartmut, in Germany what are you doing regarding consolidation using somehow the same treatment as part of the induction one? So are you using systematically or not?
HG: The results of the treatment after high dose therapy mean consolidation is very interesting. We have the situation that the insurances will not pay this kind of treatment in our regular patients, they’re paying only for the low dose thalidomide as maintenance in patients not achieving a CR. We have to do, for patients with high risk features, after first or second autologous transplantation to ask the insurances if they are willing to pay for two or three cycles VDT or whatever. The majority of German patients don’t get consolidation treatment because we have not enough data to go to the insurances and to say, “OK, this is standard of care for young myeloma patients.”
PM: So you need evidence based, which is not so bad in fact. Well, we are convinced, for example, in France of the role of consolidation and even if we are lacking data, I fully agree with you, we are using systematic consolidation outside clinical trials with the VTD regimen, the same regimen that we are using up-front. What about you, Pieter, in your centre in the Netherlands what are you doing? Systematic consolidation? I mean outside the clinical trial setting.
PS: Yes, I see your point. I feel close to France in this point because often we have the feeling that the response after high dose melphalan and autologous transplant may improve further if we were to apply consolidation therapy. I have to say there’s no randomised trial showing the benefit of consolidation therapy. In your group you did two phase II trials, one with and one without consolidation and the results are clearly better with consolidation so we feel tempted sometimes to apply consolidation. Within the trial, current trial, we are investigating the role of consolidation so we are not giving it routinely at this time to patients who are not in a protocol.
PM: And so you mentioned, Hartmut, that you are using thalidomide in maintenance only in patients who are not achieving CR.
HG: That’s correct.
PM: And you are not using lenalidomide maintenance, not using bortezomib maintenance, because the drugs are not approved and not reimbursed.
HG: The situation that we have now is that we have this opportunity to use lenalidomide in a big trial; it’s in a good situation for our patients. And then we have the situation according to the common study with the ? group; we have results for patients with bad cytogenetic features that the long term administration of bortezomib would improve the progression free survival and overall survival. This is a subgroup analysis and not the primary endpoint of the study. On the other hand, the improvement in overall survival is around from 20 to 60% after three years and this is a huge amount of benefit. Therefore, for high risk patients we’re asking the insurances to pay for bortezomib outside of a trial and mostly they are saying yes.
PM: So in France we are never using maintenance outside clinical trials. No bortezomib, no thalidomide and no lenalidomide because the drugs are not approved and we are lacking data showing an overall survival benefit. So what about you, Pieter, in the Netherlands? Systematic maintenance outside clinical trials or no maintenance or in the middle, in some patients only? What is your opinion?
PS: The same position as in France.
PM: No maintenance at all?
PS: No maintenance outside clinical trials.
HG: I’m not really agreeing. Your study group have published also good results for subgroups and, in my view, it’s not clear to separate every time between consolidation and maintenance. The maintenance also increases the amount of the drugs and the tolerability is not so good on the other hand. In my view it’s not only maintenance and consolidation, there’s a grey zone between both decisions.
PM: So maybe the last comment from the three of us regarding the treatment, common treatment, let’s say, of young patients outside clinical trials frontline. So I can give you the example of France, we are using VTD, three to four cycles, high dose treatment and then consolidation with two cycles of VTD and no maintenance. These are the French recommendations in 2013. What is your standard of care, let’s say, outside clinical trials for the majority of the patients?
PS: Since thalidomide and bortezomib have been approved for use in first line, we have two regimens, in fact, for induction which is VCD, like in the trial, and VTD like you have, for four to maybe six cycles followed by high dose melphalan, autologous transplant and no consolidation or maintenance at this time.
PM: OK, and to summarise?
HG: In Germany we have also two induction regimens, one is the same as in the ? Group, in Dutch, it’s VCD, and the other part is PID. And then we mobilise stem cells after three cycles, transplant one time, not achieving CR second autograft, and then not achieving a CR then we use thalidomide.
PM: OK. So thank you very much for these recent updates on the routine treatment, let’s say, in the Netherlands and in Germany. Thank you very much. So bye bye everyone, see you tomorrow for day three in Kyoto.