Debate Regarding Upfront Treatment of Immune Thrombocytopenia

ITP experts debate different strategies they use in upfront treatment of ITP.

James Bussel, MD: Tell us about how you think rituximab should be used, up front or close to front?

Caroline Piatek, MD: Rituximab has remained in the refractory setting for ITP for some time. It has also been studied in combination with other therapies such as high-dose dexamethasone in patients with newly diagnosed ITP who initially showed a strong overall response rate, sometimes up to 100%. When you go out to about a year, you’ll see that response rate drop to 60% or so, but we see still the good initial response. The problem we have with rituximab is the infectious risk, which I’ll come back to in a second. Certain sets of patients tend to respond better to rituximab, notably young women. So up-front steroids—dexamethasone and rituximab—remain an option for some patients in the up-front setting.

James Bussel, MD: If you measure immunoglobulin levels ahead of time and they’re normal—maybe I’m wrong, but I think there’s very little infectious risk with rituximab in the patients with ITP. We definitely need to discuss COVID-19 too because that’s incredibly important. In at least 1 of the studies, Nichola Cooper and I had 44 or 45 patients whose immunoglobulin remained normal. We have to worry about hepatitis B, but that’s become a much smaller issue lately because there are several treatments you can give if you need to.

PML [progressive multifocal leukoencephalopathy] is incredibly worrisome as well, but as far as I know, there was only 1 well-documented case of PML after rituximab and ITP. That case was very atypical. In the initial series in Blood in 2012 there were all kinds of malignant hematologic patients with the median time from rituximab to development of PML being about 6 months. The 1 case of ITP was over 3 years, and there were a number of intervening treatments. Lastly, in certain populations, even MMF has had risk of PML associated with it. In general, I don’t worry much about infections after rituximab, other than COVID-19, which we’ll come back to in a minute. What do you think Craig?

Craig Kessler, MD: I’m not a great fan of up-front rituximab. We’re all guided by our personal experiences, and I’ve had several patients who’ve received multiple cycles of rituximab because it didn’t work up front. I’ve seen several cases of individuals who developed severe immunodeficiency syndromes. This is something that needs to be brought up frequently when you consider placing patients in a complete response without rituximab. We have an 80% response rate with TPO plus dexamethasone up front with short cycles of dexamethasone. You can save the rituximab for the secondary ITP or the refractory ITPs rather than put it up front. My preference is not to use rituximab up front.

James Bussel, MD: There’s a lot of debate about this. If Terry Gernsheimer was on the call, she’d say that it was hard for her to see patients with ITP who hadn’t received rituximab already because it’s widely used. I agree with you about the multiple cycles, but I left out something important. In our experience, when you gave 3 cycles of dexamethasone with rituximab, you had about 20% of patients whose immunoglobulin levels did go down some and maybe 10% for whom they went down severely. We have used IVIG replacement in those patients for a very short period until their Ig-G recovered, but that’s debatable in certain settings as well.

Transcript Edited for Clarity

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