Mikkael Sekeres, MD, MS: There is also a discussion about comorbidities. These patients are starting with their MDS [myelodysplastic syndrome] at a median age of 70 or 71 years. There’s a large discussion about competing risks in MDS. A person’s risk of dying is not just because of the MDS; it’s also, at least in Ohio, because of things like heart disease, and blood pressure, and diabetes, and a host of other things that people have.

Ellen K. Ritchie, MD: Well, also the interesting fact that many of these mutations that we talk about in MDS have a correlation with cardiac risk. We’re at the beginning of understanding what the relationship might be of a person who has CHIP [clonal hematopoiesis of indeterminate potential], for example, and has a DNMT3A, for what their cardiac risk may be. These patients probably have cardiac risk—all up front with the availability of these mutations. But we haven’t fully investigated what those are.

For the 71-year-old patient, you have a whole gamut—71 is a number, but in the older age group, number may not be so important. You have a 71-year-old who’s running 5 miles a day. For that patient, if you look at the recent New York Times article about aging and muscles, that person may have the muscles of a 25-year-old, but their age is 71 years old. But then you also have a patient who has been smoking for 40 years and may be on intermittent oxygen; they may also be 71 years old. Or even a diabetic who has had many complications of their diabetes who’s 71 years old. That patient is a much older 71-year-old than a 71-year-old who is physically active. Number isn’t everything. You have to look at how fit that patient is and their overall ability to perform their life’s activities.

Mikkael Sekeres, MD, MS: I feel like I’m the opposite. I have 71-year-old muscles most days.

Ellen K. Ritchie, MD: We have to do some work on that as hematologists, right?

Mikkael Sekeres, MD, MS: Does that influence your treatment decisions about patients? Let’s put transplant aside because with transplant you have a comorbidity index score that you can calculate on the basis of comorbidities and the outcome of transplant. But, in your day-to-day decisions about treating patients with common drugs for MDS, do comorbidities influence that, or do you just go ahead and treat away?

Jamile M. Shammo, MD: I think it’s hard to distinguish from the performance status—deterioration may be arising from the disease itself. If you have someone who is anemic and has a hemoglobin of 7 requiring transfusion, perhaps treating the disease will improve that. But it’s different if you have someone who may have CKD [chronic kidney disease] and rising creatinine which may influence the dose that we are about to give. That’s a different story, and I think that distinction needs to be made.

Mikkael Sekeres, MD, MS: That’s a good point.

Rami Komrokji, MD: I think there are patients for whom you will actually start the treatment because of the comorbidities. For somebody who is having unstable angina when they are anemic, usually we may wait until somebody is below a hemoglobin of 8 or 7 to treat. But if somebody is having a comorbidity that improving their anemia will make…better, you may actually treat earlier. Sometimes the choice of treatment and dosing is adjusted based on the comorbidities.

Ellen K. Ritchie, MD: The other factor here is, for me, when we start a patient on an HMA [hypomethylating agent], we’re asking these patients to come monthly to the clinic to receive 7 days of azacitidine. It is a commitment that that patient makes long term to a treatment. I also look carefully at what the caregiver status is for that particular patient and what their ability is to actually make that commitment to come every single month in the first couple of months to be able to come in regularly, potentially to need transfusions until the therapy starts to work. It’s complicated when you’re actually figuring out the treatment plan. For a 90-year-old woman who is fit who has a 95-year-old husband who’s taking care of her and is driving her back and forth to the clinic to be able to get these therapies, you really have to think about how feasible that is. You need to have a real discussion with your patient as to what the commitment will require.

I find that to be more and more of an important aspect. Who’s going to take care of them? Who is around for that patient? Are they able to make the commitment to come in as frequently as they need to if they have a fever or come in for IV [intravenous] antibiotics? You have to know that information up front. You have to really know your patient before you make the commitment to treatment.

Mikkael Sekeres, MD, MS: I think that was beautifully stated because these are long-term commitments. These are therapies that require people to come in to a treatment center frequently, and these are older individuals who have spouses who are older individuals as well and may have other medical conditions that they’re trying to manage at the same time.

Transcript Edited for Clarity