Use of HMAs for the Treatment of MDS

EP: 1.Myelodysplastic Syndrome Diagnosis and Risk Assessment

EP: 2.Clinical Considerations in the Diagnosis of Patients with MDS

EP: 3.The Impact of Mutational Status on Treatment Considerations for MDS

EP: 4.Staging Models in Diagnosis and Risk Assessment of MDS

EP: 5.Individualized Treatment for MDS

EP: 6.Guidelines for the Treatment of MDS

EP: 7.ESA Use in the Treatment of MDS

EP: 8.Luspatercept: An Erythroid Maturation Agent in MDS

EP: 9.Treatment of Transfusion Dependent MDS

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EP: 10.Use of HMAs for the Treatment of MDS

EP: 11.HMAs in High-Risk MDS

EP: 12.Role of Transplant in MDS

EP: 13.Treatment in Older Patients with High-Risk MDS

EP: 14.Emerging Role of Venetoclax in the Treatment of MDS

EP: 15.Promising Data for Pevonedistat in High-Risk MDS

EP: 16.Unmet Needs in High-Risk MDS

Gail Roboz, MD: Nothing works. You have your patient. You tried everything, you had an ESA, you've been flagging this bone marrow with some cytokine support, some len, some len plus cytokine, some Eltrombopag. You're going to an HMA. My transition is to high-risk disease but I'm just asking one specific question. Is the low-risk patient who is going on a hypo methylating agents, a refractory cytopenia, ongoing transfusion dependence, is that a low risk patient Rami?

Rami Komrokji, MD: I'm not sure, so as I mentioned, I first like keep it to the last option for the lower risk or every now and then if cytopenia is really forced me, it's not thrombocytopenia. I'm not sure they are low at risk. They probably have high risk disease in my mind at that point because they've gone through different treatments and we've looked at this also before like after HMA that in the lower risk, what we call lower risk, the middle survival was 18 months for that to go. You almost see this fail, even if they are not progressing to a higher risk disease after HMA's, they, it's a total different story. My take on that is I keep it as like my last effort or unless this cytopenia has forced me to use it, I tend to use obviously the 5 day regime's and sometimes we have some data now and hopefully we'll see randomization for the consortium study that we did on three days even in the lower risk. I tend to be using it as the last effort in lower risk. Actually, in smaller subset of patients, like if they are young and early in the disease will probably mention, I am a fan of cyclosporine, although there is so much discussion about that. But in younger patients, early in the disease for cytopenia's, I prefer to go out of cyclosporine versus hypomethaning agents.

Gail Roboz, MD: Interesting, I mean they think that a lot of us have, we kind of dabbled in that for a long time with the hypocellular marrows, and I still, I agree with you there, I'm not sure I've done it on a high cellular marrow, but I think the point that I was trying to kind of force, which I think we've said in different ways, is that somehow in MDS, there are these buckets, your low risk, your high risk and it just doesn't work like that. This disease is very, very complicated and there are patients for whom that risk stratification and I think all of us have said this in different and Azra said it literally right out of the gate, that the app doesn't exactly tell you what it going to happen with the patient. The application of hypomethylating agents has been typically in the high risk column and the reason for that is because of the data that led to the support of the hypomethylating agents with respect to hopefully slowing down rate of progression to AML, hopefully a survival benefit in addition to things like transfusion independence and quality of life. Those were really for the high-risk patients. Are we saving anybody's life with the hypomethylating agent if they are not having increased blasts? I would say that's relatively controversial. You were very clear that for a lower risk patient, this is going to be your last resort of what to do but in a higher risk patient, everybody probably agrees, that patient is in trouble if you have or if you're meeting the criteria that Azra said, the bad mutations, the increased blasts, the bad site of that's a life threatening disease. Whether it is meeting criteria for AML or not, so Azra, let me start with back to you then, so this is the patient that you talked about originally, this is the patient who is in some mortal danger, who is not going to be able to go on with a little bit of this and a little bit of that, how do you, how are you thinking about that patient with respect to starting an HMA, the timing of starting an HMA and what will you select? Which one?

Azra Raza, MD: Gail, since this is supposed to be a discussion, I'm going to ask you a question first before I answer this because you've gotten away with only asking questions.

Gail Roboz, MD: Listen, I-

Azra Raza, MD: But I know you're too well a doctor to let you go away without expressing something that I needed advice about. I am dealing with say, a 47-year-old white male who has been leading a perfectly healthy life. Sudden on a CBC for some injury or something, he's found to have a hemoglobin of like 10 grams. Platelets are 140,000 so it's likely low. We do a bone marrow and clearly, it's dysplastic. He has low-risk MDS, and he has normal cytogenetics and a genetic mutational profile shows type 2 mutation. Something about this guy who's only 47 is worrisome to me. I'm seeing him every month and now I start to see that he's dropping his gowns. Of course, I get a transplant consult and, of course, they find a match, but they say, we're not going to transplant him because he's low risk. I know that he's in this liminal space which is in-between. He neither belongs to high-risk nor to the low-risk. The question you asked about, when do we initiate hypomethylating agents, do I wait for him to now become transfusion-dependent? Do I wait for him to drop his platelets below 50,000 or so? When do I initiate? That's a question you asked me about a very clear-cut, high-risk patient. That's easy to decide. The decision to start HMA always depends on can the patient get a transplant or not, and then is the patient eligible for an experimental trial? If those two are gone is then we start HMA. That's my rule, but I want to ask you, what would you do with my patient who is in this liminal space right now, who's heading for the worst?

Gail Roboz, MD: I think that it really, really highlights well this just isn't a disease of columns and boxes. For that patient, in particular, I would say that depending on the transplanter you sent that to, I could certainly find five transplanters in five minutes who would take that patient right in. It's interesting because I agree with you, there is some discussion among the transplanters. Some of them will actually do their own IPSS and take a look and say that they're not going to take somebody in that early because that forbid the patient has a toxicity of transplant, then they're going to be accused of, well, why are they taking somebody in early for an upfront risk of mortality in 30 days, that's not zero when they have low-risk disease? There are plenty of transplanters who I think are quite anxious to take a patient with a lot of dysplasia in.

Transcript edited for clarity.