How Is the MDS Patient Experience Measured?

A roundtable discussion moderated by Guillermo Garcia-Manero, MD, of the University of Texas MD Anderson Cancer Center, focused on the latest updates in lower-risk myelodysplastic syndromes (MDS). The panel included Jamie Koprivnikar, MD, of the Hackensack University Medical Center; Solly Chedid, MD, of Singing River Health System; and Thomas LeBlanc, MD, MA, of Duke Cancer Institute.

In the next roundtable segment, the panel discussed how to measure the MDS patient experience and whether it’s time for new endpoints in MDS.

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Dr. Garcia-Manero: In [MDS], measuring survival is not usually the primary endpoint because patients with lower-risk disease have relatively long survival. As Solly was saying, we’re really looking for improvement in hemoglobin. Of course, you would like this to translate into improvement in quality of life (QoL) and clinical well-being of patients. I know this has been challenging to measure in the context of phase III trials, but how do you see this issue of measuring patient experience? How do you think that these new compounds impact this fundamental phenomenon of what we want to do with these drugs?

Dr. LeBlanc: It’s such an important question and a tough one to answer, but I think it’s the most important question, especially if you’re the patient. What am I going to feel like and what will it be like if I do treatment A versus treatment B? The treatments may not be equivalent in how often you have to receive them, how long they’ll work, or how much they will change the hemoglobin, but they may also not be equal in symptoms and side effects that are caused. So, we always have to have hard endpoints like treatment-free remission, which these trials are often powered to transfusion-independence like on COMMANDS for at least a 12-week or longer period.

For the patients, QoL also matters, and we haven’t always been able to measure this in a meaningful way in clinical trials. Not just in MDS, but across cancer care. The European Medicines Agency requires some QoL assessments and uses these to make regulatory approvals and recommendations for therapies. The US Food and Drug Administration says that they do it or want to do it a bit more, but it’s always felt a bit debatable how much value they place in these measures.

Even the measures themselves, when they’re well-validated measures like the EQ-5D, give you good overall QoL data in domains about things that matter to people. Can you do your activities of daily living? Are you having pain? Are you having significant symptoms? Are you able to do other things that you want to do to function and enjoy life? We don’t always see clear benefits on those scales in these trials, and yet when we all are treating these patients, it does feel like we’re seeing benefits.

When you see and treat somebody with MDS and they go from needing transfusions, one or two units of blood every one to two weeks to not needing any blood for a month or a month and a half or two months, and the time keeps getting longer, it’s life-changing for those people. It may not get rid of their symptoms, and it may not improve their health-related QoL on a stringent measure that assesses only the things that it assesses.

So, I think we should be devising ways to include measures of things like time toxicity. How often did you have to come to the clinic? How many hours did you have to come to the clinic? How often did you have to sit in the chair for half a day after getting pre-meds and then having to take a nap while you let your antihistamine wear off if you’re getting that pre-transfusion, especially for the folks who’ve had prior reactions? How long did you have to drive? How much did you have to pay in gas money and pay for parking? It’s a big challenge. It impacts people’s lives and well-being.

I’m excited to see some new efforts to measure these kinds of things not as much on big, randomized phase III trials, but to explore doing these TWiST kinds of analyses—time without symptoms and toxicity or other kinds of time toxicity assessments. I’m hoping we can figure out a way as a community to standardize these and make them part of what we do in our trials. But, we’re not there yet.