How Advances in Genetic Profiling Are Affecting Myeloma Therapy

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Please remember the opinions expressed on Patient Power are not necessarily the views of MD Anderson Cancer Center, its medical staff 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.

Andrew Schorr:

Hello and welcome to Patient Power. I’m Andrew Schorr.  A leading expert in myeloma on a world stage is Dr. Gareth Morgan.  Previously, he was in the United Kingdom, and now he’s at the University of Arkansas. He’s director of the Myeloma Institute there and helping lead research. He joins us now. Dr. Morgan, thanks for being with us.  Now your institute at Arkansas has been a leader in gene expression profiling for myeloma. Tell us about that program, how it’s expanding and how that has impact for targeted therapy for myeloma.

Dr. Morgan:

So gene expression profiling has been a major tool I would say in being able to understand the biology of myeloma, and it's very good at defining molecular subtypes, high- and low-risk behavior, and I think now it can supplant the testing called FISH and cytogenetics and provide a complete alternative to that approach. 

It's generally available and I think very important for people to understand what their molecular sub-group and risk status is. 

Going forward, I don't think it provides all of the information that you need, so we've been developing an approach called next generation sequencing or whole exome sequencing to identify the patterns of mutation at the DNA level present within individual myeloma patients.  

And at least one of the lessons we've learned from that is that a pathway called the Ras/MAP kinase pathway, which is a growth factor signal, so it makes the cells grow, is mutated. 

So what's the point of knowing that?  Well, there are now drugs that specifically target Ras and downstream of Ras, so for patients with those mutations or activation of that pathway, drugs called MEK inhibitors or BRAF inhibitors can function. And we know because we've treated patients that it works. 

They're nontoxic, some skin rash, but actually this is an important way forward because irrespective of the bad genetics in the cells you switch off the signal pathway, and the cells commit suicide. 

So it is a treatment.  It's cutting edge.  But really I think the excitement about it is if you can do it for one pathway, there are going to be other pathways that can be targeted.  And so I think this acts as a signpost as the way forward.

Andrew Schorr: 

So would these different treatments be incorporated into the total therapy tandem transplant protocol, or would they be separate? 

Dr. Morgan: 

So total therapy is a concept, okay, and the concept is changing with time.  So it's—total therapy means giving combinations of treatment up front, investigating all of the biology of the disease, and now we're starting to integrate targeted treatment as well. 

And so what we're trying to do is to capitalize on the benefits that total therapy brought in terms of these long-term survivors and cures but at the same time trying to kind of improve outcomes but reduce the toxicity. So it is well-known that the total therapy program involves a lot of chemotherapy. And so if we could reasonably change that chemotherapy without losing the benefits that we've gained, I think it's going to be very good for patients. 

And in the context of that, these new antibodies therapies that work by totally different method to chemotherapy look very exciting. And if we could, you know, either add to the benefits of chemo or supplement some of the blocks by an antibody block, I think we'd be making significant steps forward. 

Andrew Schorr:

Dr. Morgan, you’ve been at this for a while on two continents. Are you hopeful now for myeloma patients?

Dr. Morgan: 

It's a really exciting time currently for myeloma patients.  I have no doubt that, you know, there's targeted treatment, all of which are these smooth—small molecules that target specific pathways.  But perhaps the thing that's closest to improving outcomes are what you might think of as immuno-oncology, so using anti-CD38 antibodies, using elotuzumab, something that activates NK cell activity. 

And there's another number of other antibodies, and you can almost imagine a whole immunologic approach to the treatment of myeloma, which in other diseases has kind of revolutionized their outcome. And I think we're at the border of doing that for myeloma. 

Andrew Schorr: 

Dr. Gareth Morgan from the University of Arkansas for Medical Sciences, thanks for being with us on Patient Power once again.

Dr. Morgan:

Oh, thank you. 

Andrew Schorr: 

I’m Andrew Schorr. Be sure to be signed up for alerts on our website, so you’ll know as we post interviews with experts like Dr. Gareth Morgan. Remember, knowledge can be the best medicine of all.

Please remember the opinions expressed on Patient Power are not necessarily the views of MD Anderson Cancer Center, its medical staff 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 August 20, 2015