Updates in the Treatment of Myelodysplastic Syndrome - Episode 7

ESA Use in the Treatment of MDS

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The panel of experts discusses considerations necessary when recommending treatment with erythropoiesis-stimulating agents in patients with myelodysplastic syndrome.

Gail Roboz, MD: Clearly as we're discussing this, Azra said right out of the gate, anemia is kind of the major problem for a lot of these patients. We've talked about it that there are dramatic observations that can be made in functional status, you want to keep the hemoglobin up as we're transfusing. There are certainly considerations that need to come into play with respect to using chelation at least in patients who are likely to benefit more than have toxicity from it. But obviously, this whole problem is happening because we can't kick the marrow to make some red cells. So, we would like to be able to kick some red cells out so that we don't have to transfuse so much and so that we don't have to have such a long discussion of chelation. This leads us to the land of ESA's, erythropoietic stimulating agents which have been a mainstay for a long time as part of the therapy of so called low risk patients. Even if they are going to go on and go on to other therapies, a lot of time, that's the initial kick off to try to see if we can get the marrow to make more. Amy, can you just walk us through the initial application of an ESA for a patient with MDS, how do you start them, what are you thinking about and how long do you give it to work before you say, this is not cutting it?

Amy DeZern, M.D., M.H.S.: Sure, so one of the things I'm not sure we said concretely for diagnosis is I do always check a baseline erythro platen level when I'm going through the diagnostic workup. I like to have that baseline. Some people use guidance of less than 200, less than 500, I have on occasion prescribed ESA's even in patients who are a little bit higher. I also always make sure their iron replete. Because on occasion, you will find someone that's actually not. And so after those things have been tidied, I will be candid that our hospital has a formulary for ESA's and I am somewhat restricted by that. If I'm doing a second opinion consultation, I am not entirely prescriptive about which specific brand agent it needs to be. But, I usually assess the degree of anemia. My personal number is around 9 but as we all keep eluding too, these things are very individualized based on how symptomatic the patient is or isn't. And then I plan a very regular schedule. We happen to use Darbepoetin, that's what is available here in Baltimore which we don't have to get into that discussion. But, I usually start it every three weeks, hit 100 or 200 and I try and do it for 12 to 16 weeks in a patient who is not densely transfusion dependent to really see if we can push the boundaries and make sure that I give them time to respond. And it's not weight based dosing, it's fixed dosing and I want to give it the proverbial college try. Because, as we all know, we don't have as many agents as would be ideal and I don't want to burn through something to quickly. I'm not still giving it at a year if they're still getting red cells monthly. So that's where I try and sit the bounds.

Gail Roboz, MD: And James, do you feel, because I definitely feel like I got patients who are you know, it's kind of once they get started, they seem to just be on it forever without necessarily responding to it. Do you feel similarly to Amy? Is your college try duration in that sort of zone of time?

James Foran, MD: Yes, after eight weeks, if I'm not seeing you know, if you're trying to maintain somebody at 8 or 9 grams, then you can continue and you can call that success if they are staying the same. But, if they are starting the transfusions after eight weeks, I'm actually adding Neupogen to patients. Kind of like the Swedish style with low dose weekly Neupogen to try to get that little extra 10% bump and you might get some combination ESA GCSF.

Gail Roboz, MD: Even after, just for the RARS or everybody?

James Foran, MD: No, I mean I think that data was not specific to RARS and so I've done that if people are not responding. At four weeks, I'll bump them from 40,00 to 60,000 of Procrit for instance and then after four months if they are not responding and they are transfusion dependent, I will sometimes add Neupogen to them or else we're moving on to another agent. I don't continue them if they are not clearly responding to the agent though. I see that done all the time. I don't think that's money well spent.

Gail Roboz, MD: OK, and Azra, just sense from you. Are you combining granulocyte stimulating factors with ESA's routinely or in any subgroups prior to abandoning therapy with those as not working?

Azra Raza, MD: I have never done it Gail, because giving GCSF is not being completing benign in my hands. People do the act often with a lot of aches and pains and things like that. In the past, I did it something like 20 years ago when the group practice was initially becoming very, very fashionable. But I really didn't see any great responses and there weren't many studies to support. As you mentioned earlier, RDRS, there was some suggestion that you can bump it from 30% to 40% or 50% response, but I do not use GCSF.

Gail Roboz, MD: I think the field has indicated pretty loudly, which I think is a good thing that growth factors don't cause AML. So, I think that's kind of an important thing to bring out there that the MDS patients should not be denied cytokine therapy for that reason, and I think while even if you're using GCSF, you might see two blasts pop up, that's not causing AML, that's kicking out to blasts from the marrow. So, I do think that's an important point and I think we're all saying similar thing, that ESA's are certainly mainstay of therapy. Plus, or minus the addition that there might be selective cases that benefit from GCSF. James, I think you're using it possibly more routinely than the rest of us but maybe not. I think that not being on them forever is the right thing because why have a patient who needs to get a shot forever?

Transcript edited for clarity.