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News From Edinburgh Myeloma 2017: What Is Double-Hit Myeloma?

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Published on November 8, 2017

At the Myeloma 2017 meeting in Edinburgh, Scotland, over 100 researchers and experts met to discuss new evidence, insights, therapies and approaches that have important clinical implications for patients and their care partners.  In this program, hosted by Jack Aiello, Dr. Keith Stewart of Mayo Clinic, Chair of the Myeloma 2017 Committee, shares three of the major themes from the meeting including new tools for bone marrow biopsies, the transformation of immunotherapy, and improvements in imaging technologies.

Myeloma2017 coverage is a Patient Empowerment Network program produced by Patient Power. We thank AbbVie, Inc. and Celgene Corporation for their support.

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Transcript | News From Edinburgh Myeloma 2017: What Is Double-Hit Myeloma?

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.

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.  Welcome to this Patient Empowerment Network program.  Recently at the Myeloma 2017 Meeting in Edinburgh, Scotland, a group of researchers and experts met together to discuss new evidence, insights and therapies for myeloma patients and their care partners. 

Joining me now is Dr. Keith Stewart.  He's Dean of Research and Vasek and Anna Maria Polak Professor of Cancer Research at the Mayo Clinic in Arizona.  He serves as chair for the myeloma 2017 committee.  And in that role, Dr. Stewart, can you kind of summarize what the highlights were that are most hopeful for patients going forward? 

Dr. Stewart:

Yeah, sure.  I'll be happy to, Jack.  Thanks for having me on again.  The three, I think three of the major themes that came from the conference were, first, the transition from using bone marrow to make an assessment of the disease status to starting to use liquid biopsies, as we call them, or peripheral blood samples.  It's still in the research domain, but we do anticipate seeing this enter clinic over the next year or two, and I think that will be of some benefit to patients to avoid what sometimes are an unpleasant experience having a bone marrow done. 

The second theme was very strongly around the area of immunotherapy, which is transforming cancer care in general and myeloma in particular.  Specifically, a lot of excitement remaining around CAR-T cells but beginning to see the appearance of therapies called (?) bites, which are essentially doing the same thing, to train the patient's T cells to find their myeloma and attack it. 

And I think the third theme was around improvements in imaging technologies which are more sensitive to pick up multiple myeloma in patients.  So those were some of the highlights of the meeting.  There were many others.  We talked a lot about certain therapies, some of the new drugs coming along like venetoclax (Venclexta), which is proving profoundly useful in about 20 percent of myeloma patients with the chromosome 1114 translocations.  So those were some of the highlights. 

Jack Aiello:

I saw a tweet that referred to something called double-, even triple-hit myeloma.  Can you explain what that is? 

Dr. Stewart:

Well, I've been thinking about this for a while.  So we've been struggling to more accurately define who has what we call lower high-risk myeloma for some time.  Low-risk and quite easy to define, but when we look at the high-risk group, these are patients whose myeloma doesn't stay in remission as long and become a little bit harder to treat more quickly.  And we find that we have some broad categories that we can put those patients into.  But within those categories there are some patients who still do very well, and so we probably cause them unnecessary anxiety. 

Then there are patients who don't do well within that group who we think need different types of treatment if we're going to make progress to improve their outcomes.  The doctors who look after a very similar cancer in the lymph nodes called non-Hodgkin's lymphoma some time ago coined the phrase "double-hit lymphoma."  These are lymphoma patients with two specific genetic mutations. 

They have now been taken out of the pool of lymphoma patients, and they are treated differently than the rest.  The rest are put in a pocket that we would call, you know, neutral or standard, non-Hodgkin's lymphoma, and they can be cured with conventional therapy.  And those who are double-hit are harder to cure and more likely to need a transplant and are treated differently from day one. 

We haven't been able to do that in myeloma, because we haven't really captured that distinction clearly enough.  At the meeting, Dr. Morgan in particular from Arkansas and from his work in the United Kingdom showed quite clearly that when you use sophisticated genetic techniques you can define a group of myeloma patients who either have two genetic abnormalities or sometimes three, which confer a worse prognosis or a more difficult disease to treat. 

And I thought it would be helpful for the myeloma community started referring to that as double-hit or triple-hit myeloma, because the oncologists around the country recognize that name from their experience in lymphoma. And it would allow us to segregate the group of patients that the drug needs to target specifically with new and different therapies, a much more clean definition of who has high-risk disease. 

Jack Aiello:

And have those therapies been developed yet, or do they still need to be developed, or do you look at whatever therapies work for certain mutations? 

Dr. Stewart:

We think that the standard therapies are not good enough for that group of patients.  So there's a group of patients who would be more willing to try a more experimental approaches early, and perhaps these are the patients that get immunotherapy very early in their treatment course or the ones in whom we use new drugs more quickly.  But they are the group with the greatest need, and I think this is why defining who they are, not over treating people who don't need special care and not undertreating those patients who do need a more aggressive approach has been a challenge for us. 

We all know it.  We've talked about it for years that we need to do this, but I think it's only now through the work of like the CoMMpass Study for the Myeloma Research Foundation, for example, where we have a thousand patients study the diagnosis and relapse, but it's only now we can really tease things apart well enough to understand who those patients are and make this next step into more precision, targeted, individualized therapy. 

Jack Aiello:

That's great.  I always look forward to seeing you at least once a year.  I run into you at ASH, the American Society of Hematology conference, that's coming up in just six weeks, and I wonder if you have any insights or can provide any thoughts about patients might be getting more excited about at ASH. 

Dr. Stewart:

Well, I—the abstracts are not public yet, so I can only comment on the ones that I know about, because I'm involved with or there's a press release about. 

We will hear update on carfilzomib trials.  One, the ASPIRE trial, which has already been published, showed that people stayed in remission longer using carfilzomib (Kyprolis) with lenalidomide (Revlimid) and dexamethasone (Decadron), or Kyprolis and Revlimid as their trade names.  We will get an update of that which shows that in fact it also improved overall survival by about nine months on average. 

We will see the results of once-weekly carfilzomib versus twice weekly a carfilzomib, and that will show that once weekly actually is as good if not slightly better than twice weekly, which is going to be great for the convenience of patients. 

And we will learn more about CAR-T cell therapy.  We will have an update with more patients with longer follow-up to see how CAR-T cell therapies progress.  And I suspect we'll see lots of updates from some of these large Phase III clinical trials which have been maturing and getting longer follow-up and more accuracy in the results.  I think we'll see quite a lot of that. 

Jack Aiello:

And just to clarify for patients, with respect to their once- or twice-a-week carfilzomib, is that at a higher dose, the once-a-week? 

Dr. Stewart:

The once-a-week dose of the study was 70 milligrams per liter squared.  That's—and it was compared to the FDA label dose which is 24 by 27 milligrams per liter squared, so it's basically a higher dose once a week than giving it separately twice a week.  A confounding factor, however, are there are some other studies with some intermediate doses, which twice weekly still look pretty strong.  So it will take us a little while to dissect the results of that study, but what I think it does give us permission to do is to start using weekly Kyprolis when patients have maybe responded initially or when convenience is a factor.  

Jack Aiello:

Good.  Well, I look forward to seeing you at ASH and learning more about the latest and greatest for myeloma treatments. 

And I want to thank everyone.  My name is Jack Aiello, and I appreciate your watching this PEN program.  

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.