Updates in Myelodysplastic Syndrome - Episode 10

Erythropoiesis-Stimulating Agents for Lower-Risk MDS


Mikkael Sekeres, MD, MS: If you have a patient who has lower-risk MDS [myelodysplastic syndrome] with anemia, it sounds like the first approach is to give an erythropoiesis-stimulating agent [ESA] like darbepoetin or erythropoietin. That’s an institutional practice distinction. One is not better than the other; it’s just that some institutions contract with the manufacturers of darbepoetin and some with erythropoietin. What type of response rates can you expect to see from ESAs in patients?

Rami Komrokji, MD: In clinical studies, the response rates were in the range of 30% to 40% with those agents. Again, it depends on selecting the patient. If you look at simple models of transfusion dependency and serum-EPO [erythropoietin], if it’s serum-EPO—and let’s assume erythropoietin is more than 500 mU/mL, or patients are getting more than 3 units of blood per month—their chances of response are going to be less than 10%; on that model it was 7%.

If they’re not heavily transfusion dependent and their serum EPO is low, those chances could go up more than 50%. In real-life data, the project that we collaborated with our French colleagues on together, when they looked at a cohort of patients treated in the United States and Europe, the responses were in the range of 50% to 60%. Then there are obviously primary failures to ESA and secondary failures. But I would say it depends on the patient selection. But all over, it’s roughly around 40%, 50%.

Mikkael Sekeres, MD, MS: Is that right?

Ellen K. Ritchie, MD: Roughly half the patients are going to have a response is the way I think about it when I talk to my patients. I say we have a good 50% chance, you know? It’s a lot better than entering Powerball that you’re going to actually get a response here.

Jamile M. Shammo, MD: The only item I was going to add is that if you’re treating your patients with erythropoiesis-stimulating agents, make sure they have enough iron to support that. Check their transferrin saturation percentage and ferritin, because you don’t want to give it to someone who might not be responding or who is also iron deficient.

Rami Komrokji, MD: And appropriate dosing. Many times, I see patients still on...doses of erythropoietin treatments for MDS, and it is inadequate dosing.

Mikkael Sekeres, MD, MS: It’s an interesting topic. There have not been great studies of erythropoiesis-stimulating agents that have been conducted in MDS. So we don’t really know the best dose, do we?

Others: No.

Mikkael Sekeres, MD, MS: The US study of darbepoetin, which was published probably a decade ago, used 500 mcg every 3 weeks, and then if somebody didn’t respond after a certain amount of time—around 12 weeks, 13 weeks—then 500 mcg every 2 weeks.

The European study that was completed and just published last year with Uwe Platzbecker as the lead author, also used 500 mcg. That study was a little quirky because the actual on-study response rate was less than 20% to darbepoetin. But then with more follow-up of these patients, probably the on-study time was too short. With further follow-up that rose to 35%.

With darbepoetin, I guess we could probably say 500 mcg every 2 or 3 weeks, although I’ve heard a lot of people who use it, 100 mcg weekly or 200 every 2 weeks. It’s all over the map.

Jamile M. Shammo, MD: I’m sure it’s dose related. There have been meta-analyses that looked at the response rate. Essentially, the higher the dose, the better the response.

Mikkael Sekeres, MD, MS: What about erythropoietin, what dose do you use?

Rami Komrokji, MD: I think typically somewhere between 40,000 to 60,000 units per week. I think the Europeans sometimes tended to use higher doses originally, to go to 60,000. Then if you have a response, you go down. But in recent data published, I think the responses are not much different, between 40,000 and 60,000 as well. I would say 40,000 units is probably reasonable. Sometimes I see the dosing of 10,000 per week. I think that’s inadequate dosing a little.

But there are actually patients who even respond to 20,000 units. Sometimes we space those in real life, even the erythropoietin we may be doing every other week. But usually we start at least with 40,000 units once a week.

Mikkael Sekeres, MD, MS: That’s super. If there’s 1 take-home point from erythropoiesis-stimulating agents, it’s that they’re not at the same dose level as for kidney failure. We’re talking about doses of EPO, of 40,000 or 60,000 units a week; DARBE [darbepoetin] at 500 mcg—not these much smaller doses.

Transcript Edited for Clarity