MDS: Low-Risk Disease Treatment Options

Transcript:

Mikkael Sekeres, MD, MS: Speaking of treatment for MDS [myelodysplastic syndrome], we’re focusing a lot on patients who have lower-risk MDS. If you have somebody who has an isolated anemia—1 of the unilineage dysplasia subtypes along the red blood cell lines—what’s your initial approach to treating that person? I’ll start with Ellen.

Ellen K. Ritchie, MD: For a low-risk patient with just anemia, I’ll look at their erythropoietin levels and determine whether they would be a good candidate for Aranesp [darbepoetin alfa] or Procrit [epoetin alfa] as initial treatment.

Mikkael Sekeres, MD, MS: At what level?

Ellen K. Ritchie, MD: If their erythropoietin level is below 100, I’ll consider trying it as an option for those patients. The exception for that might be the 95-year-old who comes to me with MDS of any kind and with anemia as their primary problem. For that frail 95-year-old, I’m going to use growth factor actually to treat that particular patient. In patients who have slightly low platelet counts with anemia, I might try using G-CSF [granulocyte colony-stimulating factor] together with Procrit or Aranesp. But I always start with growth factor therapy and give it a trial for those particular patients who fit. If they have 5q minus syndrome, they’re definitely good candidates for lenalidomide, and I would consider that as a treatment for those patients. But I like to see patients fail growth factor first.

Mikkael Sekeres, MD, MS: By growth factor you mean darbepoetin or erythropoietin.

Ellen K. Ritchie, MD: Right, or erythropoietin.

Mikkael Sekeres, MD, MS: How about you Rami?

Rami Komrokji, MD: I would take a similar approach. First, I look at like the adjuvant. In most of the low-risk patients, we still treat anemia per se, so the major indication is to treat anemia. The other cytopenias can sometimes dictate your choice of therapy. If your platelets are 60 per mm³, you’re not treating for thrombocytopenia, because you could have adequate living with platelets of 60 per mm³. But it may dictate your choice a little on the treatment.

I still go through the same thing: if patients are anemic symptomatic, then I think it’s reasonable to consider erythropoiesis-stimulating agents, whether it’s erythropoietin or darbepoetin as the first step. I use serum … EPO [erythropoietin] level of less than 500 mU/mL, I’ll still give it a try for 8 to 12 weeks. If they are responding, I continue. If not, then I move to the next step.

The next step is dependent on if there is deletion 5q? Are the patients young? Or what are the concomitant other cytopenias? If patients have deletion 5q, I think lenalidomide is the standard treatment for those patients with high response rate. The NCCN [National Comprehensive Cancer Network] Guidelines actually give you the choice to go to lenalidomide directly, even without the ESA [erythropoiesis-stimulating agent] trial. We still do the ESA trial because that’s how the studies were done. It was always after ESA failure.

If patients are young, then I think an underutilized treatment for those patients is ATG [antihymocyte globulin] plus cyclosporine, so immunosuppressant therapy. In our experience, it’s not really the cellularity of the bone marrow. It’s mostly the age, and you use it early in the course of the disease. In younger patients I will use that. But that’s a smaller subset of patients.

The rest of the patients, if they have non—del 5q, they are not candidates for immunosuppressive therapy after ESA failure. Then I think our options are either going to be still lenalidomide and then deletion 5q—although it’s not FDA approved, but it’s on the guidelines to be used. I select patients that are purely anemic, good platelets above 100 per mm³, neutrophils above 1000 per mm³ to consider lenalidomide in non—del 5q. We may discuss that later on. Maybe there’s a role for combining them with erythropoietin again. For hypomethylating agents [HMA], I use them only for patients who have really thrombocytopenia or neutropenia. I like to sequence things in that I will not use hypomethylating agents on lower-risk patients unless they really have bad disease-risk features that I’m worried about or other concomitant cytopenias, so that I cannot use the other options. We’ve looked together at the sequence of therapies, and we see higher responses if we use LEN [lenalidomide] before HMA. We see this phenomenon of bone marrow failure after HMA, so I always push HMA as my last choice, unless the concomitant cytopenias won’t let me use it.

There is a very small subset of patients we see with thrombocytopenia alone. I think there are some data I know that you could consider like TPO [thrombopoietin] stimulant...for that small subset of patients from the Italian study. So that’s my overview.

Ellen K. Ritchie, MD: If there’s a good clinical trial for a low-risk patient when they failed ESAs, that’s my first choice if we are able to do that. For those low-risk patients that fail ESAs, I feel that if there is an appropriate trial, that’s a really good time to enroll a patient.

Jamile M. Shammo, MD: One thing I was going to add is that just because somebody has MDS, not all their anemia may be attributed to that. We have to make sure we rule out other causes. I’ve had patients with MDS who have iron deficiency. Treat the iron; the hemoglobin goes back to where they don’t need to be treated. So, let’s always be clinicians before being MDS doctors.

And rule out other causes…

Ellen K. Ritchie, MD: Polypharmacy in these patients also is a real problem. Although you see the patient, many other specialists are often seeing these patients. When they come back to you, they’re on a whole slew of new medicines for something else from some other specialists they saw. Sometimes these medications will cause cytopenias. I find that to be a real challenge in being a physician—reconciliation of all the medications that these patients are getting and making sure that they’re not contributing to cytopenia.

Mikkael Sekeres, MD, MS: These are such fabulous points. If you look at clinical trials in patients with MDS and you look at the control arm who received placebo, you always see a little bit of a response rate. It’s not that they actually responded, it’s that they were enrolled on study and their GI [gastrointestinal] bleeding stopped. It’s a pseudo response, right?

We see these rates of the pseudo responses in placebo arms in MDS studies that range anywhere from 2% up to 13%, 14%, 15%. I think that’s an absolutely brilliant point, that looking for other causes of anemia, we can’t just assume that it’s the MDS that’s causing the anemia.

Transcript Edited for Clarity