First-Line Treatment Options for Lower-Risk MDS

Transcript:

Rami Komrokji, MD: Maybe we can move a bit and start talking about treatment. We’ll start with the lower risk. Thomas, can you give us an overview of the lower-risk MDS [myelodysplastic syndrome] landscape? What do you think of the first-line treatment, when do you start the treatment?

Thomas Cluzeau, MD, PhD: Yes, so for the first-line treatment, there is not much approved treatment. Today there is the erythropoiesis-stimulating agent [ESA]. Based on the phase 2/3 clinical trial, [it’s been] positive and showing an increase of transfusion independency and an increase of hematological improvement, using an erythropoiesis-stimulating agent. There is also red blood cell transfusion. I think we could also discuss, an introduction, the combination of iron chelation, maybe early in the disease. For the erythropoiesis-stimulating agents, usually we have to start with symptomatic anemia, but there’s not a definition, so we need to define a threshold to start. The threshold is less than 10 g/dL, so before transfusion dependency. Usually we try, if it’s possible of course, depending on the time when we do the diagnosis of MDS, to start the treatment early, so it’s based on retrospective analysis. We are showing that if we start early with that treatment, we have a better outcome for our patient. So, today we recommend starting at less than 10 g/dL and of course if the patient is transfusion dependent.

Rami Komrokji, MD: Absolutely, and I think it’s similar in the United States that erythropoiesis-stimulating agents are still the first line that we use. Do you have a certain cutoff in your practice to start the ESA?

Guillermo Garcia-Manero, MD: Our practice is a bit different because we are a referral center. What I can tell you is that what I see in the community that refers to us is that people who have a low threshold, as Dr Cluzeau was saying, to start those ESAs, not infrequently in transfusion independent patients. For asymptomatic anemia, with someone at even 9 g/dL of hemoglobin, I’m not sure I would start an ESA right away, but with some degree of symptomatology, with some degree of anemia, I think I agree. We would try to improve erythropoiesis in those patients.

Rami Komrokji, MD: What is the dosing we should be thinking of for erythropoietin and darbepoetin at least?

Uwe Platzbecker, MD: That’s a very good question, and I think there are different opinions on that. I was first trained in surgeries, so I would start rather tough and then lower the dose. This would be my approach. I normally start with 60,000 U epoetin alfa administration every week and then potentially decrease the dose at the time of response. I think hematologists start with the lowest, or a lower dose, 30,000 or 20,000 U epoetin alfa and then escalate. I think it’s a question of philosophy and the baseline level of hemoglobin, maybe also the level of transfusion dependence, but that’s my recommendation.

Darbepoetin, Thomas mentioned the phase 3 trial, which was negative in a way that they made a mistake at the very beginning. They started with a very low dose, 500 μg every 3 weeks, and then later the dose was escalated to every 2 weeks. That would be my recommended starting dose. You can even dose-dense darbepoetin later if needed. I think a debate is always about the addition of G-CSF [granulocyte colony-stimulating factor]. Is this something you should do in the first line? I would not recommend it if you start with the highest dose, with the 60,000 U. I think the G-CSF data are mostly derived from studies where lower doses of epoetin have been used. But maybe we come to the second-line therapy, and this could be an option to rescue some patients who lose response on epoetin monotherapy.

Rami Komrokji, MD: Absolutely, and the reason I asked the question is that in the United States we see a difference in the pattern of the dosing of the erythropoietin, and most of the time people are on the lower side. They use doses that are used for anemia of chronic renal insufficiency. That’s not enough. My approach is very similar to yours, I start with the higher dose, and if there is a response, then I could deescalate because that also gives you 8 or 12 weeks to know if the patient is responding or not, and they don’t waste another 6 months adjusting the dosing. Thank you.

Transcript edited for clarity.