Advances in Treatment and Management of Immune Thrombocytopenia - Episode 8

Thrombopoietin Receptor Agonists in Pediatric Immune Thrombocytopenia

, , ,

Shared insight on thrombopoietin receptor agonist (TPO-RA) use in the pediatric setting of immune thrombocytopenia management.


Morey Blinder, MD:Why don’t we move on now to the thrombopoietin receptor agonists [TPO-RA], which is a large class of drugs with now a broad experience. Not only for ITP [immune thrombocytopenia], but for some other diseases, as well, and so, I think it’s important to discuss that. I’d like to hear everybody’s experiences and understanding of the TPO receptor agonists, so, why don’t I go back to Cindy and ask about the pediatric population and the role of TPO receptor agonists. There is some approval there, so, they should be available, but what are your thoughts?

Cindy Neunert, MD: They are available. We have access to both romiplostim, as well as eltrombopag. Avatrombopag does not have a pediatric indication yet. We are quite happy in the pediatric space to have therapies that we can offer that are with a relatively low adverse effect profile compared with our previous options. Also, that may bridge patients. We know that the majority of pediatric patients are going to get better on their own, so it is really nice to have an option that we feel you can use for a short period of time. It’s not like giving them Rituximab, where you’re sort of exposing them to these big drug doses. You can kind of titrate. We don’t even titrate, we pick a goal platelet count with the family that gives them the quality of life they want, and if that’s 30,000, we go for the lowest dose that achieves that platelet count. I think a lot of us are using them much earlier in pediatric ITP for that child who has a bleeding phenotype or hasn’t quite recovered from their ITP yet. We try to avoid the ups and downs of IVIG [intravenous immunoglobulin] and repeated steroid use because we don’t do chronic steroids, we do short courses. So that leads to what I call the ITP roller coaster, and I think the TPO is at a really nice advantage of giving a stable platelet count, even very early in the disease for a child who either wants to resume activities or has a bleeding phenotype that you want to maintain a certain platelet count.

Morey Blinder, MD:Cindy, to pick your brain a little bit more, would that approach precede COVID-19?

Cindy Neunert, MD: I think it did. I definitely think COVID-19 has shifted a lot. There was a shift, as everybody has talked about, away from immunosuppressant therapies, but I think we were already going that way anyway. We’re very adverse-effect averse in pediatrics and families are very adverse-effect averse when you start talking to them about the things that may happen to their child, and these really have offered an option there that’s quite appealing. There is ongoing work to try to understand how to utilize these more up front. The indications right now are not for newly diagnosed patients, but certainly, many of us do that in our ICON 2 [ITP Consortium of North America] retrospective registry that we look back. We had about 10% of the patients that were just in the newly diagnosed phase, and that was just retrospective, off-label, clinical use. So, clinicians are using them much earlier—not waiting.

Morey Blinder, MD:Can you comment on what fraction of patients you think are then able to become therapy-free, say? Off therapy?

Cindy Neunert, MD: I think we will get some better natural history data out of some ongoing registries, but traditionally, it’s been approximately 80% of children will be better by 6 months. I’m using that old definition of chronic. What we found when we followed those patients was that, of those who had ongoing disease, about another 25% would resolve again over the next year, right? So, you’re looking at a very small number of children who go on to have persistent or chronic disease. For a lot of us, these are very appealing, even 1 month in. If you’ve got a child to whom you gave IVIG, maybe they had a response, but it wore off, or you gave them steroids, but they’re an active toddler, or they’re a teenager who’s experiencing those fatigue symptoms — these really, I think, again bring up our concerns about Rituximab. Clearly, in children, we don’t like anything that has lifelong risk associated with splenectomy, right? Lifelong is much different to a 4-year-old, so we think very differently about splenectomy and then a lot of the other agents aren’t approved, so these have really found a space.

Transcript edited for clarity.