Myeloma Roundtable: Immunotherapy, Checkpoint Inhibitors and Combination Approaches

Published on

Topics include: Treatment

This group discussion from our partner, the Patient Empowerment Network, features experts discussing news on advances in treatments for multiple myeloma from Myeloma 2015 in Boston.  Dr. Kenneth Anderson from Dana-Farber Cancer Institute is joined by myeloma experts, Dr. Rafael Fonseca from Mayo Clinic Arizona, Dr. Irene Ghobrial from Dana-Farber Cancer Institute, and Dr. Gareth Morgan from University of Arkansas for Medical Sciences. The experts review the latest novel targeted therapies, such as immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies and kinase inhibitors.  They explain how these developments are providing benefit to patients and why the outlook for multiple myeloma is so promising.

Clinical Trials Mentioned in This Video:


View more programs featuring , , and

Transcript

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.

Dr. Anderson:

So another area that’s been talked about here is that of novel targeted treatments. You know we’ve been blessed in the last 10 to 15 years we have, you know, immunomodulatory drugs—thalidomide (Thalomid). lenalidmode (Revlimid), pomalidomide (Pomalyst). We have the proteasome inhibitors, which have started out with bortezomib (Velcade) and now moved to carfilzomib (Kyprolis), and we’re hearing here about an oral proteasome inhibitor ixazomib (Ninlaro). And then we’re hearing about other novel agents that are very exciting—the monoclonal antibodies, the KREM-1 inhibitors, new kinase inhibitors are being proposed. That’s really very, very exciting I think. Maybe I can ask any of you, what of these new targeted therapies do you think really is representing a major advance and has the most promise for patients? 

Dr. Morgan:

I’m excited by targeting the RAS-MAP kinase pathway. It clearly can be functional. We’ve had some great data here from a German group talking about how mutation status doesn’t always correlate exactly with activation status of the pathway. And I think if we can pursue that to its logical conclusion, we should be able to ultimately to define who will respond to a kind of RAS-MAP kinase pathway inhibitor, minimize patient discomfort and actually get responses. 

Dr. Anderson:

Well, it’s very exciting. You know I think the other side of that is that once we define these roadmaps or circuits that are allowing myeloma cells to grow, we can figure out whether a particular medicine works or doesn’t. But even more importantly, we can figure out what side roads or what detours the myeloma cell uses to get around our treatments and allow myeloma to return.

Dr. Morgan:

So I’m quite interested in the whole apitosis pathway, so the p53 mutations with ATM, ATR and whether you could use that as an Achilles’ heel. I mean, they’re resistant to chemotherapies. But if you could use something like a PATH inhibitor and a strategy, they might be really good for that high-risk group of patients. 

Dr. Anderson:

I agree. You know, the way we think about it, you said synthetically fallady[sic], which I understand. I’m not sure the patients do though. So what I would say is it’s sort of the Achilles’ heel. We identify when we use a treatment, we know that maybe the treatment itself works or not. But it can be another Achilles’ heel that if we target that second target, then we get lethality for the myeloma cells. So I think that’s a super concept. What about immune therapies?

Dr. Fonseca:

You know, it’s just incredible to see what has happened in the area of immunotherapy, and this is across the board in cancer. And certainly myeloma’s not the exception, both by agents that simulate our immune system and then make that immune system go and fight the cancer cells as well as by indirect strategies where you just attack something directly to the latter in myeloma the development of this antibodies attack the surface of the myeloma cells. I describe it to my patients this is sort of like anti-serums, like what you would get for snake bite, etc. But it’s just that they go, and they bind straight into the cancer cells. And then our immune system’s primed to go and destroy that through various mechanisms. I think we have great promise in that, and one of the best parts is that they probably will combine well with existing treatments. So if you put the right lineup, we think there might be a future where this is going to be the winning combination for a good number of patients. And certainly other treatments such as this other monoclonal alemtuzumab (Campath), that is also having some results that are very, very promising towards harnessing our own immune cells’ ability to kill the cancer cells. 

Dr. Ghobrial:

And I think that’s the great thing about those new immunotherapies and new antibodies that are emerging now and really what’s changed the treatment of myeloma. The other thing is that they’re agnostic to the mutation. So you could have a bad mutation or a good mutation. But if you have that surface antigen that will come and allow the immune system to attack the cell, the immune cells and the new system can really attack a good myeloma or not so bad myeloma versus a very bad myeloma cell with efficiency.  And I think combination therapy plus immunotherapy would be the way to go for our patients.

Dr. Anderson:

Now I couldn’t agree more. I do have to say that we don’t use the word good in myeloma in the same sentence. 

Dr. Ghobrial:

That’s true. 

Dr. Anderson:

I’m just teasing.

Dr. Ghobrial:

Not so bad versus very, very bad myeloma cells.

Dr. Anderson:

There you go. There you go. But in terms of the immune therapies, I would just add I think the extreme power is of our God-given immune systems. You know, we get a cold one day, and we get better. And the next week, we get bronchitis, and we get better. So there’s this incredible ability to adapt and remember the different exposures to which we’ve had, whether they be infections or other noxious stimuli. And the immune system is really able to adapt. So while myeloma is also rapidly evolving and mutating and changing and progressing, the immune system I think has the ability more than anything else we have to deal with a changing enemy, if you will.  

And the other concept that I think we’ve learned from traditional chemotherapy is this of combination treatments. We talked about, you know, blocking two different pathways perhaps, Gareth. But in the immune area, we’ve already learned, and this meeting is evidence of that, so the alemtuzumab antibody that you mentioned, Rafael, is wonderful. It targets the myeloma cell. Once the antibody’s there, it’s marked for destruction. But it needs the help of lenalidomide to augment the host immune response, trigger the immune cells and stop the immunosupression and allow that antibody to facilitate those cells being destroyed.  

What is also exciting here is that things that haven’t worked in the past, like vaccines in cancers have not been by in large effective, they are going to be discussed in the combination approaches. So with lenalidomide and other combinations to just quick mention are these checkpoint inhibitors. And I think we should just spend a minute to let patients know about what those really are. So I’ll just introduce it, and I’d love to hear what you all think about the potential. But it turns out that myeloma like other cancers have this camouflage on their surface. The camouflage is called PDL-1. And the good guys are the immune cells, the T cells and natural killer cells, they’re the immune army to really marshal against the cancer, express what’s called PD-1. And when PD-1 on the immune system reacts with PDL-1 on the target myeloma, it’s a break. It’s a down-regulatory circuit. So even though the immune system’s trying to react on the myeloma, it can’t. So the breakthrough is the ability to blow the fuse, to take the brakes off by using an antibody to either PD-1 on the immune cells or PDL-1 on the cancer cell and allow the cancer’s own immune system to do what it really should be doing. And in melanoma and in lung cancer, we already have such drugs FDA approved. In myeloma, we have a very exciting session about those kinds of strategies here not only alone but in combination with antibodies or with vaccines or with lenalidomide, the immunomodulatory drug. So are you all excited about these combination immunotherapies as I am?

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.

Advertisement
Join Our Community Register for Events Read Our Latest Blog
Advertisement

Page last updated on April 19, 2016