17th Congress of EHA, Amsterdam, 14-17 June 2012EHA 17

Advances with bendamustine in multiple myeloma from EHA 2012

Professor Philippe Rodon – General Hospital, Blois, France


Philippe Rodon, you’re here at the EHA meeting to talk about your results with bendamustine, extremely interesting in multiple myeloma. We’ve been hearing about this old drug, it’s an old drug but a good one it seems. Can you tell me about the study that you’ve been doing?

We’re conducting a phase II study specifically dedicated to elderly patients in first relapse. In France the first line therapy is IMiDs and corticosteroids and sometimes with an alkylating agent and we wanted to develop a specific treatment for patients relapsing after this first line.

Now you chose older patients because of what, in this case, to try bendamustine?

Because the prognosis of relapses in elderly patients is very bad. What we showed on the IFM trials that we conducted previously that median survival of patients relapsing in progression after first line therapy was between nine and thirteen months. Then we thought that we needed to develop active therapies and tolerable therapies for this category of patients.

So typically they would get dexamethasone with perhaps either lenalidomide or bortezomib?

Yes, this is the basic regimen for these patients but we thought that we could improve the prognosis and the activity of the regimen by adding bendamustine which is a promising drug in multiple myeloma.

And we’ve been hearing, in fact, that this agent did rather well, fairly low toxicity. So what happened? What exactly did you do in your study, how many patients did you look at?

It was a phase II study, we included 73 patients in 27 IFM centres between March 2010 and July 2011. Today we just analysed the first four cycles and what we saw after this early phase of therapy is a very good response rate because we have an overall response rate of 67%, which is interesting data. We have a good tolerability too because toxicity is mild and this regimen can be tolerated in elderly patients.

Are you able to compare this to how the same patients would do on just the bortezomib-dexamethasone?

Of course we just can do a historical comparison and this cannot replace a phase III study.

Of course.

But we believe that this combination compares favourably with bortezomib and dexamethasone without an alkylating agent and, more specifically, bendamustine.

So what exactly were the results from the study?

The results of the study were 67% overall response rate, we also had six minor responses out of the 73 patients.

Which compares with what, typically, from historical controls?

It’s about 40-50% with Velcade and dexamethasone.

So certainly it’s looking, as you say, favourable.

We believe so, yes.

Obviously it’s early days but what do you think doctors might glean from your findings so far?

What I believe is that today in multiple myeloma we have three major classes of therapy: alkylating agents, IMiDs and proteasome inhibitors and what I believe is that every patient, each patient, with multiple myeloma needs to receive during the course of therapy these three classes and they can be diversely administered to patients. In France our standard therapy is to give IMiDs, corticosteroids and melphalan in first line treatment and obviously we aim to propose to patients a proteasome inhibitor in second line therapy. In order to be as active as possible it’s better to combine with an alkylating agent, for example bendamustine.

Now one of the issues we’ve been hearing about here at the EHA meeting in Amsterdam is this matter of talking with the patients, patients helping the doctor make the choice. Have you got any guidelines, especially adding bendamustine into this mix and you say alkylating agents also, how do you explain to the patient what might be the best treatment for them?

Today we do not have a specific advice about this one because we only developed in a phase II study and it’s too early of course. But we usually explain to patients that a proteasome inhibitor, and today bortezomib, is a very potent drug in relapse and that it’s better for results to combine this drug with corticosteroids and with an alkylating agent and bendamustine is a very potent alkylating agent and it’s well tolerated. Then we believe that it will be favourable for patients to receive this combination.

Now, you’ve been adding bendamustine in the setting of relapsed refractory disease in elderly patients, do you have any kind of feel for whether this agent might be useful earlier in the disease?

Bendamustine is approved in first line therapy for multiple myeloma but in a specific category of patients who cannot receive IMiDs or proteasome inhibitors because of pre-existing peripheral neuropathy. Then bendamustine is approved in first line therapy for these patients. But, anyway, in multiple myeloma bendamustine is an alkylating agent and other alkylating agents which had been developed before in multiple myeloma – melphalan and cyclophosphamide, are currently used in the treatment, in the first line treatment of the patients.

So what more further research needs to be done in multiple myeloma treatment to improve the picture over and above what you have at the moment?

First we are developing new classes of drugs, a monoclonal antibody elotuzumab which is very potent and a very interesting drug with no toxicity. We have two new proteasome inhibitors in clinical trials – carfilzomib and the MLN compound which is a novel proteasome inhibitor and we believe that these new proteasome inhibitors will be better tolerated than Velcade and for MLN we’ll have the advantage of an oral therapy which is very important for patients. We also have a new IMiD, a third generation IMiD, which is pomalidomide, actually today in clinical trials, and this third generation IMiD is able to induce responses in patients who are refractory to Revlimid. Then it’s very interesting and the landscape, the therapeutic landscape of multiple myeloma, is going to change in the future.

Well, so it seems. A large number of agents, very promising ones, very interesting ones; the monoclonal antibodies, of course, a different approach. But how does the doctor assess how much progress can be made, what are your words of advice to doctors at this point in what they should be doing now in their clinical practice?

Yes, what is critical is the stratification of patients and we are waiting for genomic techniques to give us tools in order to better classify the patients and to have a better look on what we can expect from different drugs in each specific patient. We believe that it will be the most important step during the next decade - stratification of patients according to the risk and certification according to the ability to respond to specific drugs.

And how much do you think the response rate can be pushed with multiple myeloma? How much are patient outcomes going to improve?

Today in cytoreduction before autologous transplant in first line therapy of young patients, less than 65, the response rate is about 100%. Then we cannot push more the response rate. What is critical is to prolong the response, the durability as well.

And the durability, how much do you anticipate that will improve with some of these new agents coming along and what should doctors be thinking about now to maximise the durability of those excellent responses?

Today we are not able to cure the disease but the aim of the therapy is to transform the disease, to transform multiple myeloma into a chronic disease.

And at the moment would you still go mainly with lenalidomide or dexamethasone, lenalidomide or bortezomib with dexamethasone, as your usual therapy?

Today it’s not approved in first line treatment for elderly patients but we believe that clinical trials on-going today will open the possibility of using Revlimid, lenalidomide, in first line treatment for elderly patients. It’s a very important drug and we will have results from the first trial which is today on-going probably at the next ASH meeting or the next ASCO meeting and it will be very important for first line therapy in elderly patients.

And the bottom line message coming out of all of this for doctors?

The bottom line message is that today we can provide to patients active therapies and well-tolerated therapies and we can transform the disease, this very symptomatic disease, into a chronic disease with fewer or no symptoms during a long period of time and this is a very good thing for patients, of course.

Philippe, thank you very much for joining us.