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Progress and Promise in the Treatment of MDS

Panelists:James M. Foran, MD, FRCPC, Mayo Clinic Cancer Center; Azra Raza, MD, Columbia University Medical Center; David P. Steensma, MD, Dana-Farber Cancer Institute
Published: Wednesday, Jul 06, 2016


Transcript:

James M. Foran, MD, FRCPC:
I’m going to wrap up by saying I think this has been a great discussion about the management of MDS. I’d like to get some final thoughts from you about the field and about how you look after your patients, and maybe some pearls of wisdom for community practitioners.

Azra Raza, MD: Thank you so much for asking me to give my personal experience with these patients and where I think the field is headed. It’s a very exciting time in the study and treatment of myelodysplastic syndromes. At one stage, I had started feeling very depressed that the last drug to be approved for MDS was 10 years ago, and why are we not doing better with our patients. But, you know, the devil lies in the details. For me, it’s the individual patient. Taking care of every single person who comes to the clinic becomes so important, and how can we help this particular patient. And, honestly, I feel so much better off today than I did before in understanding their disease and offering them better options for supportive care measures, and offering them disease-modifying drugs and some targeted therapies.

So, the thought of what is available now, the ability to go in and use cutting-edge, almost God-like technologies, like CRISPR—which are molecular scissors that you can use to go in and splice out mutations and correct the mutations—just the excitement in the whole area of cancer research where we can do some of these things in real-time, give the patients back their own cells with their corrected stem cells—those kinds of things, plus the whole burgeoning field of immune therapies that’s coming along. My one very firm belief is that all successful treatment of cancer seems to be, besides surgery, immune-mediated. This is especially true for myelodysplastic syndromes because think of what works.

For lower-risk MDS, we have lenalidomide, which is immune-modulatory. We have ATG and cyclosporine, which are immune-suppressive therapies. Then we have hypomethylating agents—which may not be acting by a hypomethylation effect, but may actually be acting by upregulating endogenous retroviruses in a cell, so that the cell gets fooled into thinking there’s a virus infection and mounts an immune response against it. And then the thing which ultimately cures MDS is supposed to be a bone marrow or stem cell transplant. How does that work? That works by having a robust graft-versus-host reaction, which stimulates the immune system. So, if that graft-versus-host reaction isn’t there, there’ll be no stimulation. And when we transplant from identical twins, often it doesn’t work because there’s no immune stimulation.

What I’m saying is that this burgeoning field of immune therapies that are becoming available—whether they are CAR T’s, or antibodies, or vaccines, or natural killer cells, or armed dendritic cells, or combinations of these—I feel that given all the panomics technology, the druggable therapies, and the immune therapies, everything that’s available makes me just feel so grateful to be alive in this moment in cancer research. I can’t believe that I have lived so long to see all this happen and evolve. So, I think it’s a very exciting time. I want to encourage everybody to participate in clinical trials, study your patients as much as you can, and give them the benefit of the latest cutting-edge technology and the best therapies.

James M. Foran, MD, FRCPC: Well, that is an eloquent final thought, or series of thoughts, that clearly means we’ll be having another panel discussion at some point. I would say there have been clear advances in supportive care, and we had clear advances in diagnostics. We have systemic therapies that work, at least for some patients, and novel combinations coming, I think, that will hopefully make an impact—some of the ones you’ve mentioned. We have to be patient. We have to treat it one person at a time. We have to give these treatments time to work. But I’m hopeful for the future, as well. On behalf of our panel, thank you for joining us.

Transcript Edited for Clarity
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Transcript:

James M. Foran, MD, FRCPC:
I’m going to wrap up by saying I think this has been a great discussion about the management of MDS. I’d like to get some final thoughts from you about the field and about how you look after your patients, and maybe some pearls of wisdom for community practitioners.

Azra Raza, MD: Thank you so much for asking me to give my personal experience with these patients and where I think the field is headed. It’s a very exciting time in the study and treatment of myelodysplastic syndromes. At one stage, I had started feeling very depressed that the last drug to be approved for MDS was 10 years ago, and why are we not doing better with our patients. But, you know, the devil lies in the details. For me, it’s the individual patient. Taking care of every single person who comes to the clinic becomes so important, and how can we help this particular patient. And, honestly, I feel so much better off today than I did before in understanding their disease and offering them better options for supportive care measures, and offering them disease-modifying drugs and some targeted therapies.

So, the thought of what is available now, the ability to go in and use cutting-edge, almost God-like technologies, like CRISPR—which are molecular scissors that you can use to go in and splice out mutations and correct the mutations—just the excitement in the whole area of cancer research where we can do some of these things in real-time, give the patients back their own cells with their corrected stem cells—those kinds of things, plus the whole burgeoning field of immune therapies that’s coming along. My one very firm belief is that all successful treatment of cancer seems to be, besides surgery, immune-mediated. This is especially true for myelodysplastic syndromes because think of what works.

For lower-risk MDS, we have lenalidomide, which is immune-modulatory. We have ATG and cyclosporine, which are immune-suppressive therapies. Then we have hypomethylating agents—which may not be acting by a hypomethylation effect, but may actually be acting by upregulating endogenous retroviruses in a cell, so that the cell gets fooled into thinking there’s a virus infection and mounts an immune response against it. And then the thing which ultimately cures MDS is supposed to be a bone marrow or stem cell transplant. How does that work? That works by having a robust graft-versus-host reaction, which stimulates the immune system. So, if that graft-versus-host reaction isn’t there, there’ll be no stimulation. And when we transplant from identical twins, often it doesn’t work because there’s no immune stimulation.

What I’m saying is that this burgeoning field of immune therapies that are becoming available—whether they are CAR T’s, or antibodies, or vaccines, or natural killer cells, or armed dendritic cells, or combinations of these—I feel that given all the panomics technology, the druggable therapies, and the immune therapies, everything that’s available makes me just feel so grateful to be alive in this moment in cancer research. I can’t believe that I have lived so long to see all this happen and evolve. So, I think it’s a very exciting time. I want to encourage everybody to participate in clinical trials, study your patients as much as you can, and give them the benefit of the latest cutting-edge technology and the best therapies.

James M. Foran, MD, FRCPC: Well, that is an eloquent final thought, or series of thoughts, that clearly means we’ll be having another panel discussion at some point. I would say there have been clear advances in supportive care, and we had clear advances in diagnostics. We have systemic therapies that work, at least for some patients, and novel combinations coming, I think, that will hopefully make an impact—some of the ones you’ve mentioned. We have to be patient. We have to treat it one person at a time. We have to give these treatments time to work. But I’m hopeful for the future, as well. On behalf of our panel, thank you for joining us.

Transcript Edited for Clarity
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