Adult Immune Thrombocytopenia Purpura - Episode 6

2019 ASH Guideline Update on Treating Relapsed/Refractory ITP

Transcript: Ivy Altomare, MD: Let’s move on to relapsed/refractory ITP [immune thrombocytopenic purpura] and talk about those other options. Ralph, you mentioned the new ASH [American Society of Hematology] guidelines. Before we talk about other therapies in the refractory setting, can you give us a brief synopsis of the guidelines that were just released a couple weeks ago, how they differ from the prior version of the guidelines, and some key highlights?

Ralph V. Boccia, MD: Sure. I think probably the 2 key highlights that I’d like to mention are 1) splenectomy and 2) the corticosteroids again, because they did have a definite focus on that. We know that the last ASH guidelines were published in 2011, and what has really changed fairly dramatically is the recommendation to delay splenectomy for at least a year to see whether that’s the patient who will go, in fact, into a remission and save the patient from that potential infectious disease issue that can be a problem later. That is now possible because of all the new drugs that we alluded to, that we’re about to talk about. That’s 1 feature.

The other is that they come down pretty strong now suggesting that we not use frontline steroid treatment for more than 6 weeks, that it should be up, and down, and off. And I like to bring up, when I talk to people, the fact that I also choose high dose pulsed dexamethasone because you almost can’t go too far. Where with the people who are using prednisone, I think it was Amit talking about it earlier, that as you begin to taper it, there can be ups and downs. We all probably find that people end up on steroids for way too long, and that’s the second thing that is highlighted there.

I think perhaps the third thing is that rituximab has fallen down the list a little bit further now that we have so many different agents between TPO [thrombopoietin] and Syk [spleen tyrosine kinase], such that although it still sits up there as an option for you in the second line or beyond, they’re recommending the TPO mimetic agents be given before rituximab. And they also highlight the chronic immune deficiency that it often puts people into as a potential risk later.

Ivy Altomare, MD: Which is absolutely true, and I think maybe under recognized, especially when patients receive a course of rituximab but then another course of rituximab upon relapse. And it’s a lot of diminishing returns with cumulative immunosuppressive effects.

Terry B. Gernsheimer, MD: Let me make 1 point about dexamethasone that I think we have to be really careful about. Elderly patients tolerate it much less, and they will do better using a lower dose of prednisone rather than blasting them. The other thing is dexamethasone at those very high doses, if we have someone who might be psychiatrically a little bit unstable, those very high doses can be very dangerous.

Ivy Altomare, MD: And certainly I’ve seen that, absolutely.

Ralph V. Boccia, MD: Good points.

Terry B. Gernsheimer, MD: So have I.

Ivy Altomare, MD: Yes, steroid psychosis, it’s no joke.

Amit Mehta, MD: On the point of the guideline….

Ivy Altomare, MD: Please.

Amit Mehta, MD: If I could make a couple of comments also, it’s interesting about the rituximab point that Ralph is bringing up because when we take a bird’s eye view about what has happened in the landscape of ITP over the past 20 years, rituximab really became part of clinical practice because we finally have something that was not splenectomy second line like the textbook used to say when we were all in medical school. It’s interesting, and I’m glad that they gradually lowered how early and how often you choose rituximab. I still feel that my observation among some of my colleagues is that it’s used a little bit more than perhaps it should because now the more and more long-term data for lack of durable responses, and relapses, and so forth down the road. So because of that, I’m glad that they adjusted that recommendation.

The other thing we saw that is tricky with the guidelines, again, as Ralph mentioned about the guidelines, they’re always lagging behind treatment options. So we have a vast number of things that are in trials and new treatments that are approved just this year, last year, and they’re not adequately incorporated into the guidelines, because it’s always a lag before they embrace….

Ivy Altomare, MD: They have to have a data cutoff. It’s not real time.

Amit Mehta, MD: I believe the current edition of the ASH guidelines just got published 2 weeks ago. Last year we discussed the fact that it was in a preliminary form 1 year ago, and the data cutoff started even prior to that. So there’s always this lag as you mentioned.

Ralph V. Boccia, MD: I’d like to mention 1 last thing about the rituximab, and that is in the guidelines also, they’re also positioning rituximab, however, before splenectomy. So they say don’t do a splenectomy before you give a patient a course of rituximab.

Ivy Altomare, MD: That’s very important

Terry B. Gernsheimer, MD: If I can add a couple of things to that.

Ivy Altomare, MD: Yes.

Terry B. Gernsheimer, MD: If you are going to use rituximab, and it is very important if you’re thinking, well, down the line if this doesn’t work I’m going to want to use a splenectomy, these patients need to be….

Ivy Altomare, MD: I know what you’re going to say.

Terry B. Gernsheimer, MD: Yes, you know exactly what I’m going to say, they need to be vaccinated beforehand. But the other thing that I found interesting, and this is the first time I’ve seen an abstract that actually was able to show this, was an increased risk of infection following rituximab therapy. There’s an abstract at this meeting, and I think that’s real important because we’ve all suspected it, but it’s not been shown before now.

Ivy Altomare, MD: Yes, we need to identify the rates and then make that knowledge known.

Transcript Edited for Clarity