Later-Line Treatment Options in Adult ITP

Transcript: Ivy Altomare, MD: I want to spend a little bit more time on these scary scenarios—the highly refractory patient, the patient who has been exposed to all of these things. TPO [thrombopoietin] receptor agonist, splenectomy, Rituxan, fostamatinib, and is still refractory. We have other immunosuppressants with a long-term historical experience, and data, to support their use: danazol, azathioprine, MMF [mycophenolate mofetil]. So I want to ask everyone on the panel, if you have a go-to of these agents, if you have a favorite, if you have a favorite combination, to help guide treatment when you have the last-case scenario where you’ve tried everything, that doesn’t seem to work.

Richard F. McDonough, MD: I think when I’ve exhausted all other therapies, I’ve certainly tried each of vincristine, cyclophosphamide, Imuran. I feel I’ve had the best response in that very refractory group with Imuran, so that’s what I’ll tend to try before some of the others.

Ivy Altomare, MD: Amit?

Amit Mehta, MD: My own approach is that my 2 most commonly used agents in that scenario are either danazol or cyclophosphamide, which are 2 of the ones that I’ve used. I’ve tried others as well because sometimes I have no choice but to keep on trying the next one.

Ivy Altomare, MD: Right.

Amit Mehta, MD: But cyclophosphamide and danazol are 2 that I’ve used more preferentially in that very refractory patient. And the important thing, we know historically that often it can take a while for them to respond, you have to keep them on the drug for a while. In the meantime also having a plan in place, of course, to make sure we’re monitoring blood counts, monitoring clinically to make sure the patient remains stable until hopefully they do get some kind of response. It may or may not happen, but you have to give it often several months to work.

Ivy Altomare, MD: Which is the deficiency of those strategies to be honest, but, yes. Terry.

Terry B. Gernsheimer, MD: Let me mention first that one of the things that we have to understand about the ASH [American Society of Hematology] guideline, is it is evidence-based only.

Ivy Altomare, MD: Right.

Terry B. Gernsheimer, MD: They excluded anything that trials were not done in.

Ivy Altomare, MD: Randomized prospective trials.

Terry B. Gernsheimer, MD: Exactly. The international consensus document, which also came out at the same time pretty much in Blood Advances actually goes through all these therapies. That is more expert guidance on how to use these.

You must try adding a very small dose of prednisone. You can start with a higher dose like 20 mg, and if they respond, get yourself down to 5 mg. And frequently they’ll suddenly have a beautiful response to it. So it’s really important to try that, perhaps before you say, this is a complete failure, and I’m going on to something else.

Ivy Altomare, MD: I meant to ask you about those data and I didn’t. So thank you for bringing it up now.

Terry B. Gernsheimer, MD: Yes, I think it’s very important to people to be aware of that.

Ivy Altomare, MD: Absolutely, it’s a great strategy.

Terry B. Gernsheimer, MD: What I would say about danazol is I have yet to find a woman who is happy with the idea of hirsutism. I pretty much never use it, never offer it to a woman. Once I’m in this kind of league of, I’ve got a patient who’s not responding to our usual therapies, I sit down with the whole gambit and I tell them, “Let’s talk about all of the adverse effects with all of these things.” We published years ago on pulsed cyclophosphamide, giving a gram per meter square, and repeating it 4 weeks later IV [intravenously]. And we had an initial 85% response rate. Our long-term response rate at 5 years was 50%.

And so in a very refractory patient I will use that. But we’ve had tremendous luck with mycophenolate. It can take up to 3 months for this drug to work, but we’ve really seen excellent responses. And then vincristine, I think people have to be careful with this because you will see a response in a lot of patients. But one of the things I’d like to say is, if you keep doing this, you’ve now got a patient who has a low platelet count and can’t feel their feet.

Ivy Altomare, MD: Precarious.

Terry B. Gernsheimer, MD: Very precarious. But I think it’s worthwhile giving 1 mg of vincristine in somebody who is very refractory, in the hospital bleeding, just to see if you can just get them safe.

Ivy Altomare, MD: That’s helpful. And Ralph.

Ralph V. Boccia, MD: Boy, Terry just covered what I was going to say, and that was, number 1, I’ll use danazol, but only in a man.

Ivy Altomare, MD: Right.

Ralph V. Boccia, MD: Then I think the high-dose cyclophosphamide is a great option. I use MMF myself. And lastly I guess is there is some published literature on even doing bone marrow transplants. Right?

Terry B. Gernsheimer, MD: Autologous, yes.

Ralph V. Boccia, MD: Autologous transplants.

Terry B. Gernsheimer, MD: But a lot of those didn’t work out so well.

Ralph V. Boccia, MD: Right.

Terry B. Gernsheimer, MD: It’s pretty toxic.

Ivy Altomare, MD: We know who to refer the patient to for that if needed.

Amit Mehta, MD: The other couple points on that, just overarching points, is that luckily between the different options we have—rituximab, fostamatinib, TPO mimetics, etcetera—there’s no cross-resistance between the 2 different pathways that are targeted. That’s the good thing we have clinically, is that we can go from 1, to the next, to the next. If they didn’t respond to the TPO mimetic, they might respond to Syk [spleen tyrosine kinase] inhibition. Or they might respond to rituximab, or splenectomy, etcetera.

Also, of course, counterbalanced with the fact that the more refractory patient clinically may have more even significant immune dysregulation, so they may be a more resistant/refractory patient anyway, but at least there’s not a cross-resistance between mechanisms of action. You can try different drugs in sequence, and hopefully 1 will hit the mark for the individual case.

Ralph V. Boccia, MD: And we forgot to mention clinical trials.

Transcript Edited for Clarity