Aggressive Treatment for Managing ITP


Ivy Altomare, MD: You mentioned earlier that a more aggressive up-front approach might lead to better outcomes, duration of response. What were you referring to?

Keith R. McCrae, MD: Well, unlike many, I am still somewhat a proponent of rituximab. I really don’t like to bring in anecdotes, but I think I’m about, probably, 4 for 6 in long-term remissions in people for whom I’ve used dexamethasone plus rituximab early in their course. Not necessarily right at presentation, but early—within 6 months of their diagnosis. Most of these people have been young people. I cannot say that they weren’t going to remit anyway, but it’s 4 out of 6 so I feel there’s probably something there. And they’ve also been on other treatments. So, when I do that, I will usually give—depending on how well they’re tolerating it—3 to 4 pulses of dexamethasone every 2 weeks, plus the standard 4 weeks of rituximab, 375 mg/m2, although the Europeans use less. In 1 case, I actually used mycophenolate for a while after that.

Ivy Altomare, MD: So, I’ll ask you the same question. Are there any upfront combinations, either emerging data or strategies, that you use? I do want to mention, specifically, recombinant thrombopoietin (TPO), because I know there was some recent data presented at the 2017 ASH Annual Meeting.

Terry Gernsheimer, MD: Yes. This was kind of an interesting abstract, although we didn’t really get what the response rate really was. But there was an abstract. Upfront they gave high-dose dexamethasone plus recombinant human TPO. They only gave the recombinant human TPO for 14 days and only followed these patients for a year. They said that the response rate was better with that versus dexamethasone alone, at a year. It is unclear how good that response really was. I’m not sure why that would be so. It’s interesting because there also was an abstract suggesting that just giving high-dose dexamethasone was giving long-term responses at a year. With so many of these therapies, we see these great responses early on. It just seems like we then look further, we follow longer, we check more patients, and it just doesn’t pan out. So, I’m not sure.

Ivy Altomare, MD: Is it safe to give recombinant thrombopoietin? I thought that was done before.

Terry Gernsheimer, MD: Thank you for asking that. This is a different recombinant than the one that everybody was up in arms about 10 to 15 years ago. At that time, what was given was a PEGylated truncated molecule. They used the PEGylated molecule because TPO has a very short half-life.

Ivy Altomare, MD: And when they gave that, it induced autoantibodies in patients. It was endogenous thrombopoietin, and then the patients…

Terry Gernsheimer, MD: It was neutralizing antibodies to endogenous TPO. And what happened was, there were actually volunteers. They were going to be platelet apheresis donors. It was really horrible. Three of those volunteers developed pancytopenia, and it lasted for years. Eventually the final patient, years later, did remit and normalize. But it was very frightening. They were down at very, very low levels. So, that was abandoned. That’s why new molecules were actually looked for, because it was felt that we just couldn’t.

As far as I know it’s only available in China right now. But it seems that the new recombinant human TPO, which I think is really absolutely identical to the endogenous molecule, appears to not be causing that problem. But we don’t have a lot of follow-up data yet. I think that we’re going to need that data to feel comfortable. But at least the molecule is not really different from the human endogenous molecule.

Ivy Altomare, MD: I do want to point out that recombinant thrombopoietin is very different from the thrombopoietin mimetics, which are analogous and do the job of thrombopoietin. But they’re not recombinant.

Terry Gernsheimer, MD: They’re binding where TPO binds or at least somewhere at the receptor. They bind in different places depending on the molecule. But they are not at all looking like that. There’s an awful lot of data about it, and nobody has seen any problems with neutralizing antibody to endogenous TPO.

Transcript Edited for Clarity

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