Ryan Haumschild, PharmD, MS, MBA: Dr Zeidan, from your perspective, what are some of the supportive care needs for patients with MDS [myelodysplastic syndrome]? Why are they important? Should those patients be considered for treatment beyond supportive care?

Amer Zeidan, MBBS, MHS: That’s a great question. Generally, we think supportive care is an integral part of treatment of any patient with MDS. However, in some patients, it could be the only therapy modality that you’re using. That generally applies for patients with lower-risk MDS. In patients with lower-risk MDS, in certain situations, you can consider best supportive care only.

When we talk about best supportive care, you’re generally referring to a few things. One is transfusions, because many patients with MDS are anemic: more than 90%. Around half of them are chronically dependent on red blood cell transfusions. That’s considered one of the supportive care elements. Sometimes patients need platelet transfusions as well. Another element is the use of anti-infective therapies. We can’t transfuse neutrophils the same way you do with platelets and red blood cells.

The only way to try to protect patients against risk of infection is the use of antibiotics. There’s a lot of controversy about using anti-infective agents as a primary vs secondary prevention modality, and there’s literature that’s conflicting. In my practice, I tend to use prophylactic antibiotics with any patient who has significant previous infection. However, in patients who’ve never had an infection, some patients do very well despite having a low ANC [absolute neutrophil count] for a prolonged period of time. This is one of the tricky areas. It requires some experience in handling this part.

The third area of supportive care for many of those patients generally includes the use of growth factors. Growth factors, depending on the literature you’re looking at, could be considered supportive care or active intervention. There are also ESAs [erythropoiesis-stimulating agents] or, in certain occasions, G-CSF [granulocyte-colony stimulating factor]. ESAs are the most commonly used drugs to treat MDS, although they technically aren’t FDA approved for this indication. Most patients have anemia, and they can improve anemia in patients, especially those who have low erythropoietin level or those who don’t need a lot of transfusions. This is one of the commonly used treatments for anemic patients with lower-risk MDS.

There are several major problems in the use of ESAs in the community. One is that patients are often underdosed. There’s a small dose of ESA that’s often used for renal disease. In MDS, because the issue is bone marrow failure, you need to give higher doses of ESA. I get patients referred to my clinic who have been getting very small doses or infrequent doses that aren’t sufficient.

The second problem is premature discontinuation. Those drugs can take up to 4 months. This is a common theme across multiple MDS drugs: they’re slow to work. Sometimes the patient is given only 1 or 2 months and then they’re deemed a nonresponder. You need to give them enough time. The third issue is the contrary of those issues: overtreatment. I have patients [who have been] on ESAs for years on end and need regular transfusions, and it isn’t clear why the ESA is being continued in this setting.

The last element is the use of iron chelation therapy, which is also considered a supportive care intervention in patients with MDS. Because of the frequent transfusions, the body doesn’t have a normal mechanism to get rid of iron. Iron will build up, and with time, it can cause damage to some of the vital organs, including the liver and the heart. It can also cause other problems. There are some data that it can accelerate progression to acute myeloid leukemia. The use of iron chelation agents needs a lot of discussion and is an integral part for patients with lower-risk MDS. However, those drugs can be tough on many older patients. They aren’t the easiest drugs to tolerate.

This is how I think about best supportive care. However, many patients with these interventions by themselves aren’t going to be sufficient. For example, with ESA, only 40% of patients would respond. If they respond, almost all patients will progress within a couple of years. Almost always, you need to get to more advanced forms of intervention active therapy. For patients with higher-risk MDS, you’re often using active therapy from the get-go. However, all these things that we discussed support the majors and are also applied to patients with higher-risk MDS.

Ryan Haumschild, PharmD, MS, MBA: That’s a great overview, with lots of supportive care management. [It’s important to] know when to move someone to more aggressive treatment or to make sure you aren’t moving them too soon because you want to make sure you’re treating that patient most appropriately. I appreciate you walking us through that. That was extremely helpful.

Transcript edited for clarity.