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Update on Myeloma Genetics and New Treatments

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Published on January 3, 2020

Key Takeaways

  • The BCMA marker is highly predictive, meaning you can predict whether a certain treatment will help, and prognostic, meaning lower levels mean longer survival.
  • Selinexor (Xpovio) is the first approved drug in a new class of treatments called Selective Inhibitor of Nuclear Export (SINE) compound.
  • Doctors are combining selinexor with other drugs like bortezomib (Velcade) in the STOMP Trial and lenalidomide (Revlimid) in Dr. Berenson’s practice.

As multiple myeloma experts are discovering more about genetic profiling and prognostic factors for myeloma, what questions should patients ask their doctor about testing? At the 2019 American Society of Hematology (ASH) annual meeting, Dr. James Berenson discusses the recommended testing to receive a genetic diagnosis and some mutations seen in myeloma. Can mutational status impact treatment outcomes? Watch as Dr. Berenson also shares research on response for patients with specific genetic markers, and how this may influence treatment decision-making.

This program is sponsored by Karyopharm. This organization has no editorial control. It is produced by Patient Power. Patient Power is solely responsible for the content.

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Transcript | Update on Myeloma Genetics and New Treatments

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.

Esther Schorr:

Where does testing come in?  Like when a patient goes in now and they have a diagnosis of multiple myeloma, whether they're newly diagnosed or they've had treatment and then there's a chance of retreatment, what should a patient be asking about in terms of testing because it sounds like a lot of it has to do with the genetic component?  

Dr. Berenson:

Yes, I mean, right now the testing that's done is pretty simplistic.  It's basically conventional cytogenetics looking at the chromosomes, whether they're abnormal or moving, and that's also done with a more sensitive technique called fluorescent in situ hybridization where you can make the chromosomes fluoresce or light up. 

Esther Schorr:

Is that FISH?  

Dr. Berenson:

FISH, yes. 

Esther Schorr:

FISH testing, okay.  

Dr. Berenson:

Yeah, that's the acronym, FISH.  But we also are moving certainly to the era of genomics, and that's becoming cheaper.  I must tell you in 2019, with one exception I'll mention in a moment, the use of genetics has not led us to patient‑specific therapy.  The exception being the Venclexta or venetoclax I talked about earlier.  Clearly as a single agent the activity is much better if you have what's called the translocation of (11;14), meaning chromosome 11 got moved to 14, which is abnormal, and that turns on the first oncogene called Bcl‑2, and this drug Venclexta is an inhibitor of that oncogene so patients who have that chromosomal marker are more likely to respond.

But in addition we are doing a lot of work now on new markers for myeloma.  Our favorite is BCMA, which I've talked about previously here.  And we know that's a highly not only predictive marker, not only prognostic marker‑‑the first meaning you can predict who on a specific treatment is going to benefit, the second meaning in general lower levels predict longer survival‑‑but really importantly are two other facts we have now in the last year. 

One is the rapidity with which if you look at the rapidity or the ability to judge responses, the old kids, which are monoclonal protein measuring the so‑called M protein, and the free light chain which is part of the antibody, those are the old ways to measure myeloma.  They've been around for years, but they're pretty slow to actually show responses. 

The new kid, BCMA, which we know is now the target of many a treatment now in myeloma among immune‑based therapy, whether it's antibody or cellular therapy, that shut off the myeloma cell.  So when it's in the blood you can track it, and the beauty is it moves really quickly because it turns over very quickly.  So you can get read on responses instead of in weeks to months and days.  So that means you don't have to keep patients on therapy as long. 

Esther Schorr:

Can patients ever stop therapy in what you're talking about?  They start and then they move to something else?  

Dr. Berenson:

Right.  So if the BCMA is that quick to determine whether you're doing well or not, we believe it can allow you to switch therapy more rapidly or perhaps add drugs in more rapidly. 

The other provocative thing we've now shown with this marker, which is a simple blood test, is that the level of it in the blood if it goes to normal levels you do amazing, even if you don't have a complete remission.  

Esther Schorr:

Okay. 

Dr. Berenson:

And I think that's very exciting.  We're presenting a lot of that data at this meeting, but it suggests that perhaps everybody with myeloma doesn't have to get every last cell out of their body.  They can actually live just fine with it.  And I'm reminded of many people in the U.S., 5 million including, may he rest in peace, my father‑in‑law, who had a monoclonal protein, so‑called pre myeloma, never got myeloma, and they're fine.  So I think we have to kind of think wider and more openly about what the end game is for treatment in myeloma.  

Esther Schorr:

Sure. 

Dr. Berenson:

Because most of the KOLs, key opinion leaders, believe you have to get rid of every last cell in every patient.  I'm not really of that philosophy.  I think we need to be smarter and more individualized on how we service patients so they live long with not only longer time but, of course, quality. 

Esther Schorr:

Absolutely.  

Dr. Berenson:

Because, you know, you can give treatments that get rid of the patient and the tumor, we'd rather just get rid of the tumor.  

Esther Schorr:

Yeah, I hear you.  

Dr. Berenson:

There are trials now going on with Xpovio, selinexor, which is a brand new class of drugs called selective inhibitors of nuclear export, and basically they plug up the holes in the nucleus so certain proteins which, generally move out, stay in the nucleus.  And when those proteins stay in the nucleus they make the myeloma cell really unhappy, poof, it dies. 

And so what people are now doing with that drug, which has now been approved recently as a single agent, they are now combining it with other effective agents such as Velcade in this trial as well as lenalidomide (Revlimid), which we're going to be starting very soon.  So the idea is to begin to combine these drugs, and again at lower doses.  And I think then we'll be able to get better tolerability because selinexor as a single agent twice a week is a pretty tough drug, but we're finding at lower doses we're finding it much better tolerated and effective when combined with some of these other drugs. 

Esther Schorr:

So in summary in all of this, Dr. Berenson, what would you say to patients who have multiple myeloma about all of these?  Is this a hopeful thing that there are so many more drugs now that can be combined?  I mean, how should they be perceiving their own situation now? 

Dr. Berenson:

It's like that old movie, it's complicated.  So it becomes more and more complicated even for those of us who see 100 to 200 myeloma patients a week. 

Esther Schorr:

Right. 

Dr. Berenson:

So I would say that you probably need to see many an expert before you decide on what your treatment paradigm is going to be because we all have different opinions, we have different ways to view it, and you have to feel comfortable. 

Esther Schorr:

So a second opinion... 

Dr. Berenson:

Yeah.  

Esther Schorr:

...maybe a third sometimes? 

Dr. Berenson:

Yeah, and maybe with people who see a lot of it. 

Esther Schorr:

Especially. 

Dr. Berenson:

Yeah, especially.  Because sometimes you may have to be treated there because they're the ones that really know how to use these new drugs in novel combinations.  That's not so true up front, but as you move along to third, fourth line of your treatment you may need to avail yourself of the opportunity to be taken care of by an expert or at least them to oversee the care that you're getting locally. 

Esther Schorr:

Well, if it was you I don't think we'd have to worry about anything.  

Dr. Berenson:

Yeah, yeah.  Thank you. 

Esther Schorr:

Well, Dr. Berenson, thank you so much for sharing this information with our audience.  And everybody, this is Patient Power, Esther Schorr from ASH.  And remember, knowledge can be the best medicine of all. 

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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