Treatment Goals for Lower Risk MDS

Transcript:Mikkael A. Sekeres, MD, MS: Let’s talk now about the current management of MDS. Jamile, what are your treatment goals for lower risk MDS patients, and when do you start treatment as opposed to just watchful waiting?

Jamile Shammo, MD: We’re talking about lower risk MDS patients who have cytogenetic abnormality versus those who don’t. Pretty much whenever they get a bone marrow biopsy and have a diagnosis of MDS, I will get an erythropoietin (EPO) level at baseline—assuming they’re not transfusion-dependent yet because obviously it could be altered with transfusion. So, I try to get it before. I might get an iron-store evaluation before I start the treatment. And then I think some of it depends on the patient and their expectations, and obviously on their level of anemia. If they’re transfusion-dependent, I think you’ll find very few people who don’t want to reverse that state. Most people would like to be done with transfusion, and they get very disappointed when they’re not. Granted, this is if anemia being the most common cytopenia in MDS—that’s my very first goal—achieve a state of transfusion independence or improve hemoglobin in those who have symptomatic anemia. In that sense, you may have a little bit of time in people who don’t have severe anemia. And, in that sense, watchful waiting may be reasonable. So, that’s the anemia part.

Now, if you’re talking about people who have different cytopenias—say neutropenia or thrombocytopenia—they’re not symptomatic necessarily, and don’t have infection or bleeding, then I would not mind watching them as well—as long as you are monitoring their counts periodically, depending on the stability of their counts. Granted, when you have a low EPO level, then certainly that will be the very first step that you would do for this. So, I think if I were to make it into big bullet points, one would be to reverse the stage of transfusion independence, and perhaps prevent transfusion need or improve quality of life.

Mikkael A. Sekeres, MD, MS: Quality of life is an interesting jumping point from that, because in lower risk patients, no therapy we have has ever been shown to prolong survival. So, we really are talking about quality of life issues. Ellen, when you think about prognosis and quality of life in your lower risk patients, how is that different for those who are dependent on transfusions versus those who aren’t? And when it is that, do you pull the trigger on starting therapy in those patients?

Ellen K. Ritchie, MD: I always have a long discussion with my patients when I am first meeting them with a diagnosis of myelodysplastic syndrome because people’s expectations for their functional status really vary. And most of the older patients really want to remain independent and not living in a nursing home or assisted living type of situation if they can help it. So, we’re really trying to find out what they want to be doing, what their level of expectation is, and what it is that they’re capable of doing. I find out that sometimes anemic patients haven’t been to their basement in 2 years where their washing machine is because it’s just too hard to go up and down the stairs. So, when you have these conversations, you actually learn a lot about their lives.

Being transfusion-dependent is really a full-time job for a lot of patients. If they require transfusions, whether it’s once a month or once every couple of weeks, it’s an all-day affair at the clinic. They’re arriving early in the morning, they’re getting a type and hold, they’re waiting for that type to be done, they’re waiting for the blood to be ordered, for the blood to come to clinic, and then they’re having their transfusion. So, they may have arrived at 9 AM. By the time they’re finished with their transfusion, it may be 6 PM at night, depending on how available their particular blood type is. And people don’t realize that it’s not a grocery store where we can just walk in and get the type of blood that they need, that sometimes it has to be ordered and brought to the clinic. It’s, I think, a real burden on patients to be transfusion-dependent, and it really is a spoiler on quality of life. And when patients are transfusion-dependent, I think it’s a real important goal to try and give them transfusion independence, if at all possible.

There are other older patients that have comorbid illnesses especially that can’t really tolerate a hemoglobin of 9.5 or 10 very well, either because they have cardiac disease or they have responsibilities in their lives like taking care of their demented husband that requires a lot of work. So, you really have to understand what the needs are of these patients and decide on how you’re going to proceed with treatment, realizing that transfusion dependence for an older patient is really extremely difficult. Not only the time in the clinic but getting someone to drive them to clinic, getting someone to pick them up from clinic, having additional blood tests in between transfusions to determine when they need it, it really is a job.

Rami S. Komrokji, MD: Yes, I totally agree. I think obviously—as you mentioned exactly, and in the lower risk at this point—our goal is to alleviate cytopenias, which is something we should think about down the road and try strive to change with more active medications, that we should be aiming to alter the natural history even in those patients. But currently we don’t, so we go by if someone is transfusion-dependent—see, I think this is something everybody is agreeing on. Other cytopenias, it depends how much they are affecting quality of life. The only couple of things I would like to add is ongoing research through the MDS Consortium—doing this study looking at hypomethylating agents in lower risk MDS—looking at randomizing patients between the standard 5 days on azacitadine and 3 days on decitabine or azacitadine. But one of the arms actually looked at patients that are not transfusion-dependent and randomized them between observation and treatment. So, I think that would be an important study to address one of those things.

The other part is now we have MDS-specific quality of life tools that we are starting to integrate in those studies, and I think those will be important because it’s always very subjective to assess the quality of life when you have good tools. I think it could be a reasonable, even target for approval for new drugs. If you show that there are new drugs that impact the quality of life substantially in lower risk patients, they could be a challenge for new drug approval in MDS patients.

Ellen K. Ritchie, MD: Well, that’s certainly been true in myeloproliferative disorders, that the approval of ruxolitinib was really based on—in large part—quality of life, and improvement in quality of life, and symptoms for patients.

Mikkael A. Sekeres, MD, MS: The tool you’re referencing is the one developed by Gregory Abel—now validated and published in Haematologica. It’s called the QUALMS (Quality of Life in Myelodysplasia Scale). So, we finally have a tool that is specific to MDS and we think really measures quality of life. I really like how you talked, Ellen, about getting to know your older patients, what their lives are like, and what their goals are. I don’t know how many of you have read, “Being Mortal” by Atul Gawande, where he talks about the end of life and how you narrow your focus more towards family, and you adjust your goals. We can’t assume—all of us who have kids who aren’t out of the nest yet—that our goals in our lives are going to be the same as our patients who are in their 70s and 80s. And it’s probably worthwhile to assess those goals during an initial couple of visits, and see what it is they do value.

Transcript Edited for Clarity