Multiple myeloma in the elderly: Expert discussion

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Published: 20 Jun 2014
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Prof Philippe Moreau and Prof Marivi Mateos

Prof Mateos (University Hospital of Salamanca, Salamanca, Spain) and Prof Moreau (Centre Hospitalier Universitaire de Nantes, Nantes, France) discuss multiple myeloma, with a particular focus on elderly patients, for ecancertv at EHA 2014.

This programme has been supported by an unrestricted educational grant from Janssen Pharmaceutica (A Johnson & Johnson Company).

PM: Hi. Thank you for joining us during this ecancer.tv programme. We are in Milano during the meeting of the European Hematology Association and my name is Philippe Moreau, I’m working in Nantes in France and I’m joined today by Marivi Mateos working in Salamanca in Spain. I wanted to ask you, Marivi, about the treatment of elderly patients; the landscape is changing very, very quickly and we are thinking that maybe in the future alkylators will be dead and we probably don’t need to use melphalan that was the standard of care, at least in combination with thalidomide or with bortezomib. So what is your opinion? You presented updated data on the Spanish study.

MM: Yes, you are right because the role of the alkylator as part of the treatment of elderly myeloma patients is now in debate because melphalan wanted to be abandoned. In line with this, in 2005 the Spanish Myeloma Group activated a trial to try to answer this question – what is the best partner for bortezomib, alkylator, melphalan or thalidomide as an immunomodulatory drug. In fact, when we published the results of this trial in 2010, four years ago, our conclusion was that VMP seems to be superior to VTP because, considering efficacy and toxicity, PFS and overall survival, there was a trend to better outcomes for patients receiving VMP. So, as the role of melphalan is a key debate at the same time we decided to update this trial and this is what I have presented here during this congress.

PM: What was the follow-up?

MM: The follow-up is six years.

PM: Six years.

MM: So I think that it’s a longer follow-up in which we have confirmed that VMP is superior to VTP as induction for elderly patients with multiple myeloma. Median progression free survival for patients receiving VMP was 32 months and median overall survival of 60 months but the most interesting data is that patients achieving complete remission, and especially immunophenotypic complete remission, achieved significantly longer progression free survival and overall survival indicating that probably VMP induced more profound responses as compared with VTP.

PM: So you have confirmed, Marivi, that the response rate is higher with a VMP combination. But into that study you had also a maintenance phase that could also explain partly the very impressive results in terms of overall survival. So do you think that we should try to use systematically maintenance? You used bortezomib and thalidomide in this specific study.

MM: I think that it’s a good question. At the present time we don’t use maintenance outside of clinical trials but I think that the future for all elderly and probably also young newly diagnosed myeloma patients will be the continuous therapy, so the prolongation of the therapy, because you’re right, in our trial after six induction cycles the patients received maintenance with bortezomib plus thalidomide or bortezomib plus prednisone. Probably the role of maintenance is influencing the longer outcome of response in our study. But, anyway, when we evaluated, when we compared VMP with VTP, VMP was superior regardless of the maintenance therapy.

PM: This is important to know.

MM: Yes. So, concerning your study conducted with bortezomib given in a subcutaneous route, an important question is can we use confidently subcutaneous bortezomib in patients with renal impairment?

PM: That was a very important question, in fact we are using now sub-cue in routine. We did a survey in Europe, almost 85% of the patients are receiving bortezomib sub-cue, not only at the time of the relapse but also as part of front line treatment. We were not that sure that the sub-cue administration was as effective as the IV one in patients with renal impairment and we know that not only at the time of diagnosis but also and mostly in the relapsed setting we do have the renal impairment issue. So we did a sub-analysis of the phase III study, pivotal study for the approval of sub-cue and we looked at a subgroup of patients with renal impairment with creatinine clearance less than 50ml/minute. Then there were 46 patients and we did compare these patients with those without renal impairment and some of them received IV, some of them received sub-cue. We showed that with the sub-cue the time to response in patients with renal impairment was shorter, two months versus three months, and also the response rate was slightly higher with sub-cue in the patients with renal impairment as compared with IV. Overall, no difference in terms of overall survival so we can conclude very easily that we are not doing any mistake with the sub-cue administration in patients with renal impairment.

MM: And concerning the renal response?

PM: Concerning the renal response we had the number of patients that we were able to have an improvement in the renal response was similar, in fact, when comparing sub-cue and IV.

MM: So I think that your results are very interesting because even unexpected results because many people are against the use of sub-cue in patients with renal impairment and your results consolidated that we can use sub-cue bortezomib in all patients without any problem.

PM: Exactly, that’s quite important in routine practice now that we have moved, almost all of us, with the sub-cue administration of the drug.

MM: That’s an important message for the community. Thank you.

PM: Thank you, Marivi, for speaking with me today and I hope you are also happy to have this discussion.

MM: Yes, thank you very much, it has been also a pleasure for me.

PM: Thank you.