DR STOCK: So this is just a pretty commonly seen patient. She’s a 77-year-old woman who came for discussion of potential treatment. She was recently diagnosed with myelodysplastic syndrome. And her hemoglobin at the time that she came to see us was 8.2, with an elevated MCV of 98, white count of 2.2 with 40% neutrophils, no peripheral blasts, and a platelet count of 79,000. Her bone marrow biopsy we reviewed. It was hypercellular. She had trilineage dysplasia with 6% myeloblasts. And cytogenetics showed a trisomy 8. She came to discuss the treatment options.

And the question is, what kind of parameters do you use for initiating treatment, and what kind of treatment would you recommend for a person like this who’s a very commonly seen patient with MDS?

DR LOVE: So Doug, how would you think this through?

DR SMITH: We start very basically, think about what are the needs? What are the patient’s needs at the moment? She’s 77, so there’s going to be some limited in long-term treatment options from the standpoint of stem cell transplant. So we say, “What are the patient’s needs as far as cytopenias? What’s the impact of the cytopenias? Are there ways to intervene that we can improve the cytopenias and improve the bone marrow function longer term?” So those are some of the early questions that we think about when strategizing for an older patient with a fairly unremarkable presentation of their disease.

DR LOVE: What other information would you want before telling us how you would manage this patient?

DR SMITH: I would want to get a sense of what’s the pace of the change of her disease, how the disease is impacting her functionally and activity wise and how much long-term follow-up have we had since the discovery of her disease.

DR LOVE: So looking at this really in a palliative model. So where does she stand in that regard?

DR STOCK: So this was a patient who actually went in for an annual physical. She had been feeling kind of lousy. She had the CBC done and then she got referred because of the anemia, the pancytopenia, and had the bone marrow done. So she’s quite fatigued. She has not yet received a transfusion, but she’s not feeling terrible. She has no fever, she has no night sweats. She doesn’t complain of anything other than the fact that she was a very functional 77-year-old woman, very active, and she just is now requiring long naps during the day, feeling poorly and wondering what the future brings.

DR LOVE: So Hagop, how would you think this through?

DR KANTARJIAN: So I think there are enough indications to treat her. She has 6% blasts, which scores 0.5. She has trisomy 8, which is intermediate, so that’s another 0.5. And she has trilineage dysplasia, so the total score is 1.5, so she’s not low risk. And so I would treat her with either azacitidine or decitabine, and I would add some growth factors in the management of this patient.

The data show clearly that either azacitidine or decitabine can improve the outcome of these patients. And she has enough indications to be treated, so I would treat her with azacitidine-or decitabine-based therapy. Now the question is, would you do something more in terms of an investigational component? And there are several studies which are looking at the addition of other things.

DR LOVE: So how would you choose between azacitidine and decitabine?

DR KANTARJIAN: I think it depends on the availability. I think they are both reasonably equivalent. One is subcutaneous, one is IV. And then the other issue is could you get it on a trial, and what combination would that trial allow you to add?

So there are a lot of potential studies that these patients could be eligible for. In the community practice, I think azacitidine or decitabine would be as good.

The other point is, she’s only 77. And so if she does fail an aza or decitabine component of therapy, I would still consider her for an allogeneic stem cell transplant.

DR LOVE: Allogeneic stem cell transplant. Hmm. Doug, agree or disagree with the entire algorithm that Hagop just outlined?

DR SMITH: I mean, he very nicely outlined the algorithm of drug development that’s ongoing and available right now. Azacitidine/decitabine plus another drug —

DR LOVE: You agree she needs to be treated or you would treat her?

DR SMITH: Yes. I mean, getting the sense that she’s really pretty physically exhausted, has some significant cytopenia. She certainly does not have low-risk disease, if you will, and she’s intermediate. And so I don’t have a problem at all treating a 77-year-old, symptomatically. We’ll often hand-hold and discuss and decide what to do next, but ultimately I think she’s going to need treatment. Her disease is going to get worse.

DR LOVE: And again, allotransplant in a 77-year-old?

DR SMITH: Nobody really knows where to cut off the age limit. It’s grown from 55 to 76 at our institution, so what’s 77 when you’re talking 76? But nonmyeloablative, reduced-intensity transplants can be delivered safely. There are studies that suggest that the up-front mortality is no different over the age of 70 versus less than the age of 70 in these groups. But ultimately, I think that you have to be very selective on who goes to an allotransplant, so performance status —

DR KANTARJIAN: So I wouldn’t consider her up front, but she does have a score of 1.5. That’s intermediate-2 disease. It’s not a lower-disk – risk disease. And so this is the kind of patients which, on randomized studies, benefited from azacitidine or decitabine.

Now, if she fails this treatment, then when patients with high-risk MDS fail azacitidine or decitabine, their median survival is about 6 months, less than a year. So one could consider the possibility of an allogeneic transplant. Now, if she fails with a low blast count and cytopenias, one could consider things like growth factors, multikinase inhibitors and others. But if she fails with a high-risk disease, I think there’s a need for consideration of a transplant or supportive care.

DR LOVE: And is allo potentially curative in this situation, Hagop?

DR KANTARJIAN: Yes, it is curative, but it’s not curative in a high proportion. So if you take a patient like her who fails azacitidine/decitabine, the cure rate is probably at about 20%. It’s not more than that.

DR LOVE: So Charlie, what do you think about the algorithm that’s starting to come out here for this patient?

DR SCHIFFER: Oh, I agree with it. I’m not sure about the transplant part in terms of her tolerance. And it’s not a question of if she responds to the hypomethylating agent, because about two thirds don’t respond. And everyone who responds, unfortunately, eventually relapses. So you have to be considering post-treatment options in everybody. This lady, I agree, will be a candidate for treatment, likely soon. But I usually watch people for a month or two. I think Dr Time, we call it, is smarter than all of us, particularly in a chronic disease like this. But given the characteristics she has, she’s likely to need treatment.

If she was a little less advanced and I would try to figure out what ails her. And what ails her seems to be the hemoglobin.

And I would certainly do an epo level to determine whether or not there’s a probability that she might respond to epo. Epo’s not going to fix the platelets. It’s not going to fix the neutrophils. She doesn’t need those fixed. What she has that makes you worry, the chromosome changes and whatever, 6% blasts, I mean. But I think we use the IPSS, but we depend more, frankly, on what happens over time, a dynamic IPSS.

DR LOVE: So I’ve been trying to predict what I think happened here, but tell us.

DR STOCK: This was about 8 months ago, actually. I picked this lady just because I think it’s important to highlight the study. She actually entered the front-line US Intergroup trial, which was a trial randomizing patients between azacitidine front-line therapy, aza plus vorinostat or aza plus lenalidomide, the early results of which were presented at ASH by Mikkael Sekeres, who was the PI of the study.

And she was randomized, actually, to the azacitidine-alone arm, the standard-of-care arm. And she tolerated the treatment relatively well, but unfortunately, after 5 cycles of treatment, she still did not really have any improvement in transfusion requirements. Her platelets have drifted down further. A repeat bone marrow exam — several have been done. And she has now about 8% blasts in the marrow. Her performance status has declined some. She’s transfusion dependent. And so the decision was to continue for another couple of cycles or to think about something else.

Chronic Lymphocytic Leukemia (CLL)

Chronic Myeloid Leukemia (CML)

Acute Myeloid Leukemia (AML) and Acute Promyelocytic Leukemia (APL)

Myelodysplastic Syndromes (MDS)

Acute Lymphocytic Leukemia (ALL)