Frontline Corticosteroid Strategies in Adult ITP

Transcript: Ivy Altomare, MD: Amit, since you mentioned first-line treatment, let’s just go ahead and talk about first-line treatment. Explain your approach with steroids. What course do you use? What drugs do you use? How often are you treating and how you do taper?

Amit Mehta, MD: Once that I decide that a patient requires therapy because of bleeding symptomatology, their platelet count has dropped rapidly and below a certain threshold that I am using in my own clinical practice, then my approach is to consider either pulsed dose dexamethasone or prednisone. My own preference is pulsed dose dexamethasone, 4 days of dexamethasone, and like Ralph was also saying about potential for rapid response, durable response, and arguably a slightly higher response rate than the more traditional lower dose, 1 mg/kg daily of oral prednisone. Those are the 2 primary options I’ll consider and I think are reasonable for any hematologist to use in practice.

My own preference is the pulsed dose dexamethasone. Primarily my decision for that preference is driven by slightly higher suggestion of response rate and also the very short course of therapy. Where prednisone, of course, is notorious for the many adverse effects and often to the point of tapering, when you are using oral prednisone, 1 mg/kg is a starting dose daily, then it can often take several weeks to taper, and even then it may not be a smooth process, as we know, because we may go below a certain threshold and they start having their platelets go down again. And then you have a situation where you may have to increase the dose again, so it may be a bumpy road as you try to taper the oral prednisone.

So because of all those reasons, I feel that the pulsed dose dexamethasone is perhaps a little bit more in favor, in my opinion, but either can be considered. Society guidelines, the ASH [American Society of Hematology] guidelines, say that you could use either/or as reasonable options, so I think a clinician could consider them. The other things that are potentially things that we might think about is do we also need to incorporate IVIg, intravenous immunoglobulin therapy. That usually will be reserved for somebody who has a more acute type of situation.

Ivy Altomare, MD: Inpatient.

Amit Mehta, MD: Inpatient, significant bleeding, surgery about to be needed, something of that nature, where we need a rapid increase in the platelet count. And there is randomized data showing that prednisone plus IVIg is superior to using prednisone plus high dose steroids, methylprednisolone, for example. Because we do have some data to inform us to say prednisone plus intravenous immunoglobulin can be advantageous to rapidly boost the platelet count. And often, clinically, that will mean that even by the next morning after starting the intravenous immunoglobulin, you should see a bump up. The patient who started, let’s say hypothetically at a 3000 platelet count, the next morning is 21,000 and may not be quite ready for the surgical operation yet, but at least they’re making their way up. Where, often within 3 to 5 days clinically, we’ll see the platelet count rise to a more acceptable level for surgical operations, 50,000, 70,000 or something higher than that.

Ivy Altomare, MD: Would you ever use or have you ever used another combination, for example, Promacta, in the frontline setting with steroids?

Amit Mehta, MD: I have not used that personally. There are data that were presented initially at the ASH conference in 2018, and in that meeting they had some data about giving Nplate with steroids up front, as well as a separate small study giving eltrombopag with steroids up front. These were not randomized studies. They didn’t have long-term outcome end points.

Ivy Altomare, MD: Certainly not a standard approach, but I just wondered what your approach is.

Amit Mehta, MD: Right. I think the bottom line, so to speak, is that it’s not quite ready for prime time, so I wouldn’t use that currently in practice. But at least it’s being explored where that may be utilized in the future. I would just say not quite right now in the setting of very small studies that we have showing us some evidence for benefit and of course not randomized data.

Ivy Altomare, MD: Right, absolutely.

Ralph V. Boccia, MD: We might just mention that the new ASH guidelines specifically do state that they do not recommend that type of combination therapy be given in the frontline.

Terry B. Gernsheimer, MD: Although, Donald Arnold, MD, MSc, just published the Canadian study that suggests that eltrombopag in a patient who is not otherwise being treated, who needs to have surgery, 3 weeks of eltrombopag was actually superior to IVIg to get somebody ready for surgery. So we have other options.

Ivy Altomare, MD: Yes. So that’s not the frontline therapy.

Terry B. Gernsheimer, MD: No.

Ivy Altomare, MD: But in the preoperative setting.

Terry B. Gernsheimer, MD: Yes.

Ivy Altomare, MD: Absolutely. Excellent point.

Terry B. Gernsheimer, MD: Which may be the first time a patient needs to be treated.

Ivy Altomare, MD: That’s true, you’re right. Before we move on from combination, we are discussing the data that are out there, and we know they are not ready for prime time, it’s not in line with current guidelines to do a combination up front, but I just want to see if there are any other studies that you have seen of upfront combinations. Because how are we going to improve outcomes in these patients? We have good therapies for second-line and refractory settings, but an upfront, more robust treatment strategy might elicit longer duration of disease remission.

Ralph V. Boccia, MD: It brings up an interesting topic, which is are we potentially better able to cure patients if we manage them in the frontline in a different way?

Ivy Altomare, MD: I didn’t want to say the word cure, but I’m glad you did.

Ralph V. Boccia, MD: Put them into remission, let’s put it that way. It’s kind of funny the way that remissions are defined by at least the ASH guidelines, it’s a platelet count of 100,000. I think we can all agree that that is a more than acceptable level. But mycophenolate has been used now with corticosteroids. As already mentioned, romiplostim and eltrombopag with corticosteroids. So it’s a topic that’s hot right now because we’re looking at earlier therapies and combination therapies with the specific notion that we would like to see whether, if we do that, we can change the natural history of this disease.

Terry B. Gernsheimer, MD: Because we do believe that the longer somebody has this disease, if you will, the more dug in that disorder becomes. As more epitopes spread, these become more and more difficult to treat, and it may be that we want to treat them hard up front. But I think we need more data for that.

Ivy Altomare, MD: The last thing about frontline therapy, because this is probably the only time that we’ll be discussing steroids. We’re going to move on to other therapies that are seen in the second-line refractory setting. But just for completion sake, Rick, can you talk about the adverse effects that steroids give, how patients feel taking them? And also if you want to comment on whether you do use separate courses of steroids in the refractory setting.

Richard F. McDonough, MD: Good question. As Terry brought up earlier, so patients, if they’ve been exposed, know what their adverse effects are, and that really leads to them to wanting to look to anything else for their treatment options. So of course we’re going to be worried about blood sugars, inducing diabetes, hypertension. We’re going to be concerned about CNS [central nervous system] effects. You’re going to have changes in depression or inability to sleep, a lot of the things that really drive people crazy, feeling jittery, feeling agitated. And so each of those are their own individual concern.

And then to your question on whether you would re-treat, and to take one step back, I do favor slightly the dexamethasone option as well up front. In certain cases, if you are 14 days, 21 days down the line and you have a situation where the count is very low, other symptomatology, I might repeat it in that situation. I will not indefinitely repeat steroid, feeling like that’s going to have less and less benefit.

Ivy Altomare, MD: And we have other things now.

Richard F. McDonough, MD: And we have other options available down the line.

Transcript Edited for Clarity