The Latest Myeloma News from the American Society of Hematology Meeting

Andrew Schorr:

Right, and Dr. Berenson, on our last program we did with you, you think transplant is history already, but related to one of the trials that I think is like phase-I/II both up front and then for people who need treatment again, it makes sense that I know Paul Richardson's group has been studying can you combine Velcade with lenalidomide, or Revlimid, another very powerful drug, and do those two new agents work better together, would that become the new standard? Do you have any feeling about that early data?

Dr. Berenson:

I would say that it looks promising. I'm concerned about side effects with that combination, particularly effects on marrow function. As I say, myeloma today is a marathon, and if we give treatments that give us amazing complete remission rates but with little marrow function left in a disease that still remains incurable, we've done a real disservice to patients. So, I think the ultimate goal here is longest life possible with best quality; that is least side effects from treatment or disease. We often miss that message when we look at large pieces of data because we're not in clinic looking at real human beings and what they're experiencing. Obviously, Andrew, you know being a patient what that can be like. So, I'm often mystified about some of the toxicities that are reported compared to what at least I see in my clinic with some of the agents that are out there today.

I think we need more data to convince me that Rev and steroids and Velcade is going to be a good and safe combination and lead to long-term, durable remissions because it's notable that some of these new agents can lead to remission rates that are extremely high, but the length of the remission is extremely brief, and in some of these newer drugs, there is some concern that we may be inducing a pretty bad, ugly clone, and I think you have to be very careful in interpreting what a complete remission means because I know, having done with Dr. Vescio a lot of molecular work to measure minimal residual disease, but these patients really are not in molecular complete remission. Complete remission here is to find an absence of protein in a bone marrow which appears to not show increased plasma cells, but we all know that this is a patchy disease, and with more sensitive testing there still remains, if you will, in the words of my old mentor, Carl Sagan, billions and billions of cancer cells left. So, these are not Gleevec complete remissions, the drug used to treat CML, where they are really very deep complete remissions.

Andrew Schorr:

Okay, let's pose this to Dr. Durie. So, Dr. Durie, we've talked in a very positive way about what came out of ASH, and Dr. Berenson is there and wondering, 'Well, okay, you can use powerful therapies, but what works best long-term?' What's your feeling about your newer agents and combining them in new ways and being able to manage side effects, and maybe you'd comment on also the data that came out about using a lower dose of dexamethasone? I think you mentioned Dr. Rajkumar, and I know I went to a news conference there. Some people are having that; Revlimid, or lenalidomide, and dexamethasone. I know he studied lowering the dose of dexamethasone and could it be just as effective, but basically, management of side effects so that somebody can really do well long term. Maybe you could comment on that.

Dr. Durie:

Right, well I think that that's obviously what it's all about. Patients want to live longer, and when we're talking about indicators, I think that a good paradigm right now is that survival is the best indicator of survival. You know, is CR an indicator? Well, I think that what we're focused now on is the patient alive early on? Is the patient alive at one year and two years? And being alive and doing well is truly the ultimate end point.

So, to achieve a good survival, we're balancing the benefit, the efficacy of the treatment, with the side effects and the quality of life, and one very interesting thing has emerged from the comparison of the low-dose dex with the high-dose dex, so that if you look at the ECOG data, the interesting thing is that is with the high-dose dex, the four-day pulses, there was a higher response rate up front versus the low-dose dex; however, if you look at the survival at one year and then at two years, it turns out that the survival was 96% at one year and 87% at two years with the low-dose dex, and so what has accounted for this difference if there was more response early on with the high-dose dex?. One is that obviously if you hit the disease harder, then it will knock it down more initially, and this has shown up in the longer-term follow-up with Revlimid/dex in the relapse setting, you need to be able to continue on therapy, and for me there was a very interesting parallel study presented at ASH by Jean-Luc Harousseau looking at the long-term follow-up with Revlimid and dex in the relapsed refractory setting with the studies MM-009 and MM-010, which were both recently published in the New England Journal, and what they commented on is that for patients who were able to reduce the dose of dex and stay on the Revlimid and dex longer term, there was I think it was 45% of the patients reached a VGPR and a CR not right away but over time, out to 12-14 cycles.

So, it's a matter of trying to have an excellent response, but how quickly do you need to achieve that, and how long can you maintain it? So, it's about therapies that can do an excellent job initially and in the short term but perhaps more importantly looking towards achieving a more chronic control of the disease to maintain that response, and I think that that's a very important new paradigm moving forward.

Andrew Schorr:

You're sounding like Dr. Berenson there. We're all running a marathon there. There you go.

Dr. Durie:

That's right.

Andrew Schorr:

Dr. Lonial, I have a question for you though. One of the things that's come up with Velcade or bortezomib is can you knock the disease way back and then just go off treatment for awhile versus with Revlimid and some of the other medicines, you know, they're pills, but you keep taking them. So, do you have any feeling about that or what discussions you have with patients about that?

Dr. Lonial:

Yes. I think there certainly may be benefits to treatment-free intervals and the absence of maintenance therapy contributing to morbidity and mortality, but I think in order to do that, you have to really get to the best response before you try and give patients sort of un-maintained remissions. I think the other piece about whether or not a patient may go without any treatment in many ways is dependent on their risk stratification. So, if you have high-risk myeloma as defined by a number of different groups, whether it's Dr. Shaughnessy's definition in Arkansas or the definition from the Mayo Clinic or other groups, there clearly are subsets of patients of a very high proliferative myeloma, and for those patients the absence of therapy may not be a good thing, whereas for other patients who have low-risk disease, they may actually gain great benefit from an absence of therapy, and so I think it's not just the depth of response, but it's also the phenotype, if you will, the biology of that specific tumor that may allow patients to either go with long treatment-free interval or stay on some type of suppressive therapy over a long period of time.

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Page last updated on November 22, 2013