Exciting New Agents for the Treatment of Multiple Myeloma

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Topics include: Treatments

[Editor's Note (12/2/2015): The FDA has approved several of the multiple myeloma treatments discussed in this interview, including daratumumab (Darzalex), ixazomib (Ninlaro) and elotuzumab (Empliciti).]

Dr. Paul Richardson from the Dana-Farber Cancer Institute joined Jack Aiello at our recent multiple myeloma town meeting to share his perspective on new treatments being studied for multiple myeloma.  Dr. Richardson discussed a number of agents, including monoclonal antibodies and how they work, immunotherapy and why these new developments are groundbreaking in the field. 

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Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you. 

Jack Aiello:

Hi.  My name is Jack Aiello.  Joining us today is Dr. Richardson from Dana-Farber Cancer Institute.  And I'm thoroughly appreciative of your being here today with us.  We want to focus on the latest and greatest with respect to myeloma, and so in that vein I wanted to ask you about what appears to be the most exciting treatment going forward, and that is the area of monoclonal antibodies.  Can you talk more about what those are and what's involved?   

Dr. Richardson:

Absolutely, Jack.  And first and foremost, it's my pleasure to be here and thank you to you and to Patient Power for kindly inviting me.  It's been a pleasure to be here at MD Anderson and with obviously Bob Orlowski and others.  

In that vein, I think that it's very exciting to sort of share with our audience I think the promise of the monoclonal antibody space.  We have now, of course, really first-in-class results from elotuzumab, a randomized study, Phase III, international, showing clinical benefit to the combination of elotuzumab, lenalidomide (Revlimid), and dexamethasone (Decadron) compared to lenalidomide and dex alone, with a substantial clinical benefit in favor of the three drugs, and the antibodies showing excellent tolerability.  And what's really compelling, Jack, is it's showing activity in high-risk disease, patients with 7 chromosome and 17 abnormalities, 414 and so forth.  

Now, why that's so important is that it validates an observation we made in earlier trials that antibodies are able to overcome the impact of adverse risk.  It's important to think about how does elotuzumab work.  Elotuzumab truly targets an immunological pathway, and it does so in a synergistic fashion when you combine it with lenalidomide, and it works primarily by turning on the patient's immune system to attack the myeloma.  

So I think it's a really tremendous advance, and I think that it represents again a kind of first-in-class moment where I think we will now have antibodies that we've been waiting literally decades for in myeloma now on the shelf for us to offer our patients.  Because I do believe it will lead to FDA approval this year for elotuzumab.  

And the other, of course, real groundbreaking stuff is the CD38 space, where monoclonal antibodies targeting CD38, which is ubiquitously expressed on the surface of myeloma but also we think may have an important role in the microenvironment of myeloma by virtue of its effects on growth and the way cells proliferate.  This is an incredibly interesting target both immunologically and in a direct sense, and no surprises here.  

Daratumumab, which has been be a phenomenal antibody, has shown single-agent activity, and when you combine it with other drugs the effects are even more profound.  

Now, validation of this principle has come from a second antibody called SAR, S?A?R [SAR650984], and I believe—and I often get the name slightly wrong but I think pronoun—it's called—it's now got a name [ixekizumab] or something along those lines, ixekizumab.  I must get it right, but SAR for short, I think has just been coined, but it's an antibody that's very similar to dara [daratumamab] but has some differences.  It's generating fantastic effects as well.  

Now, the interesting thing is, just because I think for audience members it's really interesting to note that not all antibodies are the same.  There is a third antibody that targets CD38 that's functionally or qualitatively different, and amazing in clinical trials of that particular antibody the responses weren't there.  So it tells you that not all antibodies are the same, even though they may have the same target.  

So the CD38 targeting principle is validated first by dara and now by SAR, but not all antibodies are the same, as illustrated by the third antibody, which on its own doesn't generate much of a response rate.  

It may well partner well, and in the future we'll have to see, but having said that I thought it was a fascinating piece of data to share with our audience that not all antibodies are the same.  So you have elo, one target, dara and SAR CD38.  

Jack Aiello:

So these monoclonal antibodies actually make your own immune system work better.  

Dr. Richardson:

And also attack the myeloma directly.   

Jack Aiello:

And also attack the myeloma direct directly.  

Dr. Richardson:

Yeah.  

Jack Aiello:

And there are—there is more research being done in—in making your immune system work better, right?   

Dr. Richardson:

There—oh, and a lot.  I mean, I think an important point is that what we've realized is that there's this whole new area of immuno-oncology, and it's I think groundbreaking.  It incorporates the monoclonal antibodies.  It incorporates the immunomodulatory drugs.  It incorporates now what are called checkpoint inhibitors.  

What we've realized is that cancers are always very clever at masking themselves from the immune system of the patient.  That's one of the reasons they arise, and what we found is that there are some Achilles' heels that we can go after.  

And probably the most important to date has been inhibition of these so-called checkpoints.  So if you can target the checkpoint, block it, the immune system is no longer fooled, and it can turn on and attack the tumor in question.  

Now, this has worked beautifully in certain very challenging cancers like melanoma, for example, and now other cancers and other solid tumors like lung cancer, but what we've realized in hematologic cancers is they have real promise as well.  Hodgkin's disease is one very obvious example where some really phenomenal recent data suggested benefit.  Myeloma, it's very early, and it hasn't been formally presented yet, but we do know that the PD?1 blockade mechanism appears to be bearing fruit in various settings, and we'll be hearing a lot about this at the upcoming ASH meeting in December.  

Jack Aiello:

Thank you much for all you do for myeloma patients and providing your expertise, Dr. Richardson.  

Dr. Richardson:

Well it's my—truly my privilege, Jack, and thank you.  

Jack Aiello:

Thank you.  

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you. 

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Page last updated on December 2, 2015