Myelodysplastic Syndromes: Translating Genetics to Clinical Practice - Episode 1

The Broad Spectrum of Myelodysplastic Syndrome

May 12, 2016

Transcript:Mikkael A. Sekeres, MD, MS: Hi, and thank you for joining this OncLive Peer Exchange, “Myelodysplastic Syndromes: Translating Genetics to Clinical Practice.” My name is Dr. Mikkael Sekeres. I am a professor of medicine, the vice chair for clinical research, and the director of the Leukemia Program at the Cleveland Clinic in Cleveland, Ohio.

Myelodysplastic syndromes (MDS) represent a heterogeneous spectrum of hematopoietic disorders for which allogeneic stem cell transplantation remains the only curative option. However, a better understanding of epigenetics, immune responses, and the use of next-generation sequencing has led to advances in our characterization and treatment of MDS. Our discussion will focus on the current best practices in the management of MDS and will shed light on how the latest research is likely to impact the field. Participating today is a very distinguished panel including Dr. Rami Komrokji, a clinical director, senior member, and professor of oncologic sciences for the Malignant Hematology Department at the Moffitt Cancer Center in Tampa, Florida; Dr. Ellen Ritchie, an assistant professor of clinical medicine at Weill Cornell Medical College, affiliated with New York Presbyterian Hospital in New York City; and Dr. Jamile Shammo, an associate professor of medicine and pathology at Rush University Medical Center in Chicago. Thank you again for joining us, and let’s begin.

I think the first area we want to talk about is the biology of MDS. It’s a heterogeneous collection of hematopoietic stem cell disorders, and we actually give it a plural, myelodysplastic syndromes, to remind ourselves of just how heterogeneous it is. I was wondering, Rami, if you could talk a little bit about the biology of MDS.

Rami S. Komrokji, MD: As you just mentioned, and you kind of summarized in your introduction, those diseases are really a spectrum. I think the first thing is to recognize that they are neoplastic, they are cancers—although they are a spectrum. And in the recent years, we’ve learned much more about the underlying biology, so now we know that most of those patients will have clonal disease evidenced by acquired somatic gene mutations in the clone. And we know now, actually, that there is more of a spectrum. So, now we talk about something called CHIP, clonal hematopoiesis indeterminate potential; we talk about idiopathic cytopenia of unknown significance. Some of those patients will have a clonal event, as well. And then we have the spectrum of MDS. I think those are definitely clonal disease. The hallmark of the clone is really ineffective hematopoiesis, and that’s partly because of the clone and their acquired somatic mutations in the clones. At the higher-risk disease, obviously there is probably differentiating potentials, arrest of the maturation of the cells. I think the other part that’s now also becoming more important is the role of the microenvironment. So, in addition to the clone of the acquired somatic mutations, we have immune response, we have an inflammation going in the microenvironment that contributes probably early on in the disease and to the myelosuppression observed. Obviously, this topic is very complex and can be a discussed for a long time, but that’s just a summary, and everybody else can also add to mine if I missed any points.

Jamile Shammo, MD: I have to make one comment. It’s very interesting when people say MDS does represent malignancy, and I totally agree with you. There’s a huge spectrum that we have to think about, because at times—when you think about people who have refractory anemia, for example—they may not necessarily have a defined clone, so they manifest mainly with anemia, and they don’t really have blasts. How is there a malignancy? I tend to think that, perhaps on one end of the spectrum, there’s certainly clones and malignancies and propensity for AML (acute myeloid leukemia) development, but on the other side, there is merely manifestation of bone marrow failure without necessarily having any clones. And so I tend to have an issue with just labeling all MDS cases as malignancy.

Ellen K. Ritchie, MD: It’s a very hard thing to talk with patients about because when you talk with a patient about a malignancy, they’re thinking about breast cancer or lung cancer, that it’s something that’s going to kill them very rapidly and that it has a really defined horrible prognosis. So, I think it’s very important when we talk to patients about MDS that we talk about the broad spectrum of disease and that we don’t label it as cancer necessarily. Because I think that it can almost be as detrimental to their quality of life with the disease afterward, by labeling it as such, than the treatments and supportive care that we have to give them.

Rami S. Komrokji, MD: But the other point to look at is that it took a long time to get insurance recognizing this, and that can have implications for the patient’s insurance coverage for the treatment and the medications.

Jamile Shammo, MD: That’s true.

Rami S. Komrokji, MD: In reality, yes, there are subsets of patients in whom we cannot identify clonal events. It could be limited by our technology currently, and those could be the cases that aren’t really MDS. So, yes, we don’t have to tell every patient that you have a cancer, but I think we all recognize that there are neoplastic stem cell diseases, and it took even the SEER (surveillance, epidemiology, and end results) until 2001 to recognize them and get that information on them. We don’t need to forget that part of the insurance coverage, the epidemiology of the disease, should be labeled as cancer, I think.

Mikkael A. Sekeres, MD, MS: One other aspect of this that I reflect on, we conducted a couple of studies through the Aplastic Anemia and MDS Foundation, where we sent e-mails to about 3000 patients, about 350 of whom responded to these e-mails. Now, an 11% response rate doesn’t sound like very much except when you reflect on when you get an e-mail and in brackets you see bulk right next to it, and you immediately delete it. So, in this sort of survey, 11% is actually considered pretty good. In this study, we asked patients how their MDS was first defined. For about 80% to 90% of patients, they were first told that they had a blood disorder or a bone marrow disorder. Only about 5% or 6% were ever told that they had cancer or something that could evolve to acute leukemia.

So, I totally agree that we shouldn’t blow out of proportion a patient who has, what one of my patient’s referred to as “mild displeasure syndrome,” something that’s just an isolated anemia and that person is going to live with it for a decade. At the same time, it’s very challenging for us when a person comes to us with MDS, has been told that she has just a blood disorder, and then we launch into a discussion of how we’re going to give her chemotherapy. That person is less likely to embrace the therapy and recognize the need for it, and less likely to stick with it once side effects kick in, and that could compromise that person’s survival. So, you’re right, it is a little bit of a tightrope we have to walk between reflecting on how serious this collection of diseases is versus not unduly frightening people who have a very mild form of MDS.

Transcript Edited for Clarity