ASH 2018 – Latest News and Research in Multiple Myeloma

ASH 2018 – Latest News and Research in Multiple Myeloma from Patient Empowerment Network on Vimeo.

Dr. Amrita Krishnan, Director of the Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope, shares the latest news and research that was shared at the ASH 2018 conference in the field of Multiple Myeloma.


Transcript:

Esther Schorr:

Hello to everybody.  This is Esther Schorr with Patient Power, and I’m here today at the 2018 ASH conference, the American Society of Hematology.  And I’m surrounded by, oh, 20-, 25,000 amazing researchers and clinicians who are studying hematological malignancies.  And I have about me today Dr. Amrita Krishnan.  Is that correct?

Dr. Krishnan:
That’s correct.

Esther Schorr:
And she is the Director of the Multiple Myeloma Program at the City of Hope in Los Angeles.  Thank you for being here.  So what I wanted to talk to you about today is what’s going on for myeloma patients.  What are the headlines from ASH this year?

Dr. Krishnan:
Good morning, Esther.  Thank you for the opportunity to talk.  I don’t even know where to begin.  There’s—every myeloma session has been packed, standing room only, which tells you obviously, number one, the advances we’re making and the enthusiasm regarding them.

I’d say the three biggest news really is obviously CAR-T cells in relapsed disease, and we started out just hearing about one CAR-T construct, the BB121.  Now we obviously are hearing many other companies presenting their results and other CAR-T constructs, which I think is very good for us because we can understand better both the technology as well as side effects and efficacy and understanding among different T-cell constructs.

The other big thing, I would say, antibody drug conjugates by specific antibodies.  And then the last but not least let’s not forget in terms of stem cell transplantation there was a big session this morning looking at new drugs in the maintenance setting, so specifically oral proteasome inhibitors.

Esther Schorr:
Oh, boy.  Okay.  So now I’m going to drill down a little bit from a lay person’s standpoint about what you just said.

Dr. Krishnan:
Okay.

Esther Schorr:
It’s a lot of alphabet soup.  So I know that you’ve been doing some work with the drug daratumumab (Darzalex).  It’s a mouthful, and I know that that’s a monoclonal antibody.  And can you talk a little bit about what the relevance is about that?  Because I think our audience has probably heard of it but doesn’t know what’s happening in that area.

Dr. Krishnan:
Sure, happy to.  So daratumumab targets CD38, which is a protein on the myeloma cell.  So it’s very specific in terms of attacking the myeloma cell.  Now, that protein is expressed in other things like red blood cells, but really it’s very highly expressed on plasma cells, sort of the myeloma cell per se.  So daratumumab was already approved for relapsed myeloma, both multiply relapsed as well as patients who have a first relapse in myeloma in combination with some of the other drugs we think about such as bortezomib (Velcade) or lenalidomide (Revlimid).

This meeting this year, though, the big excitement is in regards to using daratumumab in newly diagnosed myeloma.  So we already know it’s a very effective drug in the relapsed setting.  We’re familiar with the toxicity profile, and overall it’s quite well tolerated, and so now the question becomes if it’s such a good drug should we move it earlier in the course of therapy to get the maximum benefit.

Esther Schorr:
So it could be a first-line therapy.

Dr. Krishnan:
Exactly.  So it’s already approved in the first-line setting in combination with Velcade, melphalan (Alkeran) and prednisone (Deltasone), so VMP, but that’s not a regimen we use in the United States.  So there’s going to be an abstract presented Tuesday, so I can’t even tell you yet because it’s a late breaker, but we only know a little hint of it which is using daratumumab plus lenalidomide and dexamethasone (Decadron) in newly diagnosed patients.  It’s called the MAIA study, and that’s the one that we’re all waiting to hear to see is that going to establish a new standard of care in the newly diagnosed front-line setting.

Esther Schorr:
So that helps me to understand that, thank you.  So then are there other studies that you’re involved in that would be interesting for patients to know about?

Dr. Krishnan:
So there’s another study that actually was presented yesterday.  It’s called the GRIFFIN study.  That uses daratumumab in combination with sort of I would say a quote/unquote standard regimen in the United States, RVD or lenalidomide, Velcade and dexamethasone.  And what it asks again the same question.  If you add to our standard backbone another potent agent, does it even further improve the responses?  So what they presented on Saturday was very early data on 16 patients, so we need to wait more, but it just shows you the excitement around that.  And that data they presented really was around the safety and suggesting that it’s a well-tolerated combination with a very high response rate, 100 percent response rate.

Esther Schorr:
Well, that would be my question then just as a care partner myself is when you’re talking about doing those kinds of combinations of two, three, four drugs are you all looking at the combined toxicity of those things and the side effects?

Dr. Krishnan:
Oh, yes, absolutely.  So the MAIA study, for example, very specifically looked at the three drugs of daratumumab plus len-dex comparing it to the two drugs, lenalidomide and dexamethasone, so–and the same thing with the GRIFFIN study.  That also was randomized so half the people got daratumumab in combination, the other half just got the standard RVD.

And there was, to be fair, a lightly higher increase in side effects when you added the daratumumab, a bit more infections and a bit more blood toxicity, so lower white counts.  So it is something to sort of, you know, take as a note of caution too, when you add more drugs that you do certainly expect that you are going to get more toxicity.  And obviously it becomes does the benefit outweigh the potential risk.

Esther Schorr:
As usual.  So I guess the other question I have is where does stem cell transplantation fit in all of this, or does it?

Dr. Krishnan:
So obviously I have a somewhat biased opinion.  I come from City of Hope, which is the largest transplant center in California, and two things I could say in terms of myeloma.  So we do over 8,000 transplants a year in the United States for myeloma, so it suggests that it’s a standards of care backbone of therapy.

As a transplanter I would say transplant still has the longest track record in terms of remission length and even if you compare it to standard RVD chemotherapy you get a longer remission when you throw transplant into that mix.  And I think what will be of interest to us is further improving upon that by either different maintenance strategies or induction strategies, so new treatment before the transplant as well to further improve the outcomes of the transplant.

And then the other thing I should mention, this is not a study that is open yet but it’s a study that we actually had some meetings about through the BMTCTCN, so a cooperative group of transplant networks, trying to ask the question.  So this is a group—you know, I used to chair the myeloma committee, and I’m still on the committee—we try and look ahead.  Right?  So we say, what can we do as a strength of network of transplant centers that patients really need?  What is the question they want to ask?  And one of the unmet needs is high risk-myeloma.  So whatever we do right now, and there’s been data presented at this meeting too, we need to do better.

For those patients who have advanced stage of myeloma, high-risk cytogenetic abnormalities, the therapy we have right now is still not optimal.  And one of the things that we’re going to do that we’re very excited about is we’re going to open a study that we’re literally going to go home and start writing in January, using CAR-T cells after an autologous transplant for patients with high-risk myeloma.

Esther Schorr:
So that gives—that’s hope for patients that have not had any real viable treatments till now or durable ones.

Dr. Krishnan:
I think that durable is what we would say.  So we’re all very excited about that.  It’s going to harness our strengths as transplanters, our strengths in cellular therapy and CAR-T and moving it up front.

Esther Schorr:
Good.  Well, thank you, Dr. Krishnan for all the work that you and your associates are doing.  I know that it’s, especially for myeloma patients and their families, it’s so important.  So thank you.

This is Esther Schorr from San Diego at the ASH conference.  Remember, knowledge can be the best medicine of all.

On the Horizon for Multiple Myeloma

ASH 2018 Conference Coverage

Dr. Elisabet Manasanch, Assistant Professor Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center, shares what’s the latest and on the horizon for Multiple Myeloma.

ASH 2018 – Multiple Myeloma Highlights

A Multitude of Options in Myeloma

Dr. Robert Orlowski, Director of Myeloma and Professor in the Departments of Lymphoma/Myeloma and Experimental Therapeutics at The University of Texas MD Anderson discusses the multiple myeloma highlights and what patients can be excited about from the ASH 2018 meeting.


Transcript:

Esther Schorr: Hi there. This is Esther Schorr from Patient Power coming to you from ASH 2018 in San Diego, and I have with me today Dr. Bob Orlowski who has joined us at Patient Power before. He’s the Director of Myeloma and Professor in the Departments of Lymphoma and Myeloma and Experimental Therapeutics—that’s a very long title—at the University of MD Anderson—University of Texas MD Anderson. Sorry.

Dr. Orlowski: Thanks very much for having me.

Esther Schorr: I’m glad you’re here again.

Dr. Orlowski: It’s a pleasure to be back on Patient Power.

Esther Schorr: Thank you, sir. So what’s going on in myeloma now at ASH? What are the highlights? What are patients going to be excited about, and what are you excited about?

Dr. Orlowski: One of the exciting areas is definitely talking about the different therapies that are targeting what’s called BCMA or B-cell maturation antigen. This is a protein on the surface of myeloma cells, and the excitement about it is it’s a target which is almost only on myeloma or normal plasma cells, not on other kinds of tissues. And that’s important because if you want to target for immunotherapy, you don’t want that target to be on too many normal cells, or the immune therapy will kill those cells and cause side effects.

So there are really three categories of drugs now that are looking very attractive. One is what’s called an antibody-drug conjugate. So this is a plain old antibody that has another chemical attached to it, and it’s given usually IV right now, attaches to the myeloma cell. It then gets inside the cell and the drug is released. So the antibody is essentially like a carrier molecule.

Esther Schorr: Kind of like a cruise missile?

Dr. Orlowski: Sort of like that. I like that analogy, yes. And then it blows up, using that analogy, the cancer cell once it’s inside.

So one of the first of these drugs that already is in the clinic is showing a 60 percent response rate in very heavily pretreated patients. The registration study, meaning the trial that hopefully will get it approved by the FDA, has already finished enrolling, so we’re hopeful that maybe by the end of 2019 this drug as a single agent will be available. And it’s really easy to give. It’s IV once every three weeks, which is pretty darn good.

Esther Schorr: And what’s the drug called? I’m sorry I missed that.

Dr. Orlowski: Well, it’s a good question. Actually, it doesn’t have a name yet, which is why I didn’t tell you what it’s called, but the abbreviation for it is GSK 916.

Esther Schorr: Okay.

Dr. Orlowski: And the reason for that is it’s actually quite expensive to come up with a name, because they have to find a name that, first of all, is not confused with other drugs so that it minimizing errors and also one that us poor feeble-minded doctors will remember so that we prescribe it often.

Esther Schorr: We’re not sure how you can remember all the letters anyway. Okay. So that’s one. Is there something else going on that you got to share?

Dr. Orlowski: So a second category of drugs that target the same protein, BCMA, the first formal presentation of those data were shown here at ASH, and this is what’s called BiTE or Bi-specific T-cell engager. And it’s sort of is a molecule, if you want to use the cruise missile analogy, that has two war heads. One end binds to the cancer cell. The other end binds to the patient’s own T cell, brings them together and the T-cell attacks the cancer cell. So it’s a way to use immune therapy with the patient’s own immune cells, and there are reports here of the first one of these which is called AMG 420. Again, doesn’t have a name yet, but it’s showing in very heavily pretreated patients complete responses with MRD, or minimal residual disease, negativity, which is really exciting.

Esther Schorr: So and that’s different than—and we’ll probably talk about it in a minute—that’s different than CAR-T.

Dr. Orlowski: Exactly.

Esther Schorr: Okay. So we can talk about that in a minute.

Dr. Orlowski: Yeah, that would be great. So the next topic is the CAR-T, also against B-cell maturation antigen, or BCMA. It’s a little more complicated though because what you have to do is you take out the patient’s own T cells and then in a laboratory you infect them with a virus. The virus has a gene in it that expresses a receptor on the T cells so that they can better recognize the cancer cells.

Esther Schorr: An invitation.

Dr. Orlowski: Exactly. Kind of. I like that.

Esther Schorr: Okay.

Dr. Orlowski: And then you infuse the cells back into the patient. They find the cancer cell, they attack it, and they kill it. So it’s great, because it’s personalized. It uses the patient’s own T cells. The problem is that it takes two to four weeks to manufacture the cells after they’ve been taken out of the patients, and so in the meantime the myeloma can sometimes be creeping up. So that’s one problem.

And also there are activities with the disease or with the T cell against myeloma, but there are also some side effects like cytokine release syndrome. But the response rates with some of the more advanced molecules are in the 90 to 100 percent range, and the durability of that is at least a year to 18 months, depending on what patient population you look at. And those are the most mature data of the three categories of immune therapies that we’ve talked about.

Esther Schorr: So of those three are any of them being looked at for first-line therapy, or these are at the moment still for people who have relapsed or are more difficult cases?

Dr. Orlowski: Right now it’s more for very advanced disease, but there are already trials planned with all three of these technologists in earlier patients and some in newly diagnosed patients, especially those with high-risk disease, because they still don’t do as well with standard therapies that we have. So it’s really an exciting time because these are some of the best results we’ve had in very difficult to treat patients, which means they should work even better when we give them earlier.

Esther Schorr: So one other question then. What’s happened to stem cell transplants for multiple myeloma patients? With all of these new combinations of treatment s, where is that in the mix of consideration for treatment?

Dr. Orlowski: Stem cell transplant is still considered part of the standard of care for patients with newly diagnosed myeloma, and in some cases it can be used for relapsed disease, especially if the patient had a really good durable benefit with a first transplant. The advantage of the stem cell transplant right now is that it with works very well, the toxicity profile is very well defined, and compared to a CAR-T cell it’s actually relatively cheap. But as the technology hopefully becomes cheaper and more available there would be great interest in comparing outcomes of people getting chemo plus a transplant, for example, versus chemo plus a CAR-T cell.

Esther Schorr: So it sounds like there’s a lot more options that are coming up for multiple myeloma patients. Is there anything else that patients that are listening would want to know about, that they should feel good about?

Dr. Orlowski: Well, there’s a lot more data with other immune therapies including earlier use of daratumumab (Darzalex), which is an anti-CD38 antibody. One of the presentations, which is still to come on Tuesday, shows the data of that drug with lenalidomide and dexamethasone in previously untreated patients, and the results really look excellent. So that will probably be one of the new standards of care for transplant ineligible patients. And there are studies ongoing with daratumumab in transplant eligible patients as well.

Esther Schorr: That’s a lot.

Dr. Orlowski: And that’s not all of it, but I think that may be all we have time for.

Esther Schorr: Thank you so much, Dr. Orlowski, for being with us again and making this a little more comprehensible for us normal mortals.

Dr. Orlowski: Thank you very much.

Esther Schorr: This is Esther Schorr coming to you from ASH. And remember, knowledge can be the best medicine of all.


Please remember the opinions expressed on Patient Empowerment Network (PEN) are not necessarily the views of our sponsors, contributors, partners or PEN. 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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Dr. Gareth Morgan, Director of the UAMS Myeloma Institute, discusses new oncogenes in myeloma and importance of testing at the time of myeloma diagnosis to set a treatment plan at the American Society of Hematology (ASH) Conference 2017 in Atlanta.

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ASH 2017 Roundtable: Multiple Myeloma Research News and Updates From an Expert Panel from Patient Empowerment Network on Vimeo.

At the 2017 America Society of Hematology (ASH) annual meeting, a roundtable of myeloma experts share breaking news and the expansion of the treatment armamentarium in and implications for different disease status. The panel includes:

  • Dr. Carol Ann Huff of Johns Hopkins University School of Medicine
  • Dr. Sagar Lonial of Emory University School of Medicine
  • Dr. Suzanne Lentzsch fof New York Presbyterian Hospital/Columbia University Medical Center
  • Jenny Ahlstrom, President and Founder of Myeloma Crowd

Myeloma 2017 Main Takeaways For Patients

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PEN Board member, Jack Aiello, leads an expert panel discussion on new insights, evidence, and therapies in multiple myeloma that have come out of the Myeloma 2017 in Edinburgh, Scotland. The panel includes:

  • Keith Stewart, M.B.Ch.B. Chair, Myeloma 2017 Scientific Committee; Carlson and Nelson Endowed Director, Center for Individualized Medicine
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  • C. Ola Landgren, MD, PhD, Chief, Myeloma Service, Memorial Sloan Kettering Cancer Center