Rituximab or Platelet Transfusion in ITP

Transcript: Ivy Altomare, MD: Amit, we talked about rituximab earlier. I just want to circle back to rituximab, so that we can for completion sake talk about the data behind the use of rituximab. What are the response rates? What is the duration of disease stability after a course of Rituxan on average? What do we know?

Amit Mehta, MD: That’s a great follow-up from the previous comments about the potential long-term durable remission.

Ivy Altomare, MD: Exactly.

Amit Mehta, MD: That’s probably the biggest reason why hematologists, I would argue, should consider the medication for a given patient, albeit the long-term response, durable response, has not been great, as we’ll describe in a second. But because there is potential for that long-term durable remission, it should at least be explained to the patient that that is a potential option. Just like we may even bring up a splenectomy even if we may feel for that particular patient, that may not be our first choice or a preferred option for that individual.

Rituximab, like we were saying earlier, really came to the fore when we finally got it on the market for various other conditions, and we started using it as one of the few things we could finally use and not use splenectomy in the early 2000s. And often the response rates early on are somewhere in the 50% to 80% level for having a platelet response, varying definitions of response of course, you know, 30,000 or 50,000, etcetera.

A couple of the biggest studies that we now know as many years have gone by with rituximab on the market, there’s 1 randomized trial from Europe, mainly from the Scandinavian region I believe, but published in The Lancet now about 4 years ago, 2015. And they saw that there was, in spite of early responses in a similar fraction of patients, in follow-up roughly I believe 5 to 7 years later, 70% had relapsed afterward. So that being said, the flip side of that is that there were 30% who maybe had a durable response, so therefore it might still be part of our armamentarium, but a significant number are relapsing and perhaps more so than we thought 10 years ago.

There was also another publication in Blood in 2012, United States data, that showed that a 5-year mark only 20% were still in stable response as well. That’s where we have to understand the limitations of it. The other big thing with rituximab, again, harking on some of the discussion we talked about earlier is the infection risk potential, and even general adverse effect risk. Rituximab as we know, as hematologists know from extensive clinical experience and various malignancies and so forth, has the potential for reaction risk, infusion risk, etcetera, with the medication. So what was presented at the ASH [American Society of Hematology] meeting in 2019, is that when they looked at patients who got eltrombopag compared to getting rituximab, there was roughly about a 23% to 25% relative decrease in risk of infection in that trial.

Ivy Altomare, MD: That was the VA [Veterans Health Administration] study.

Amit Mehta, MD: The VA study, yes. I think that’s fascinating and it maybe confirms what we were guessing clinically, but again, good to see the data are there. And that’s a real thing. Rituximab, we’ve long known it has prolonged immunosuppression effects. Often the way I usually explain it to patients is the effect can go for 6 months or more. And in the meantime patients can incur serious infections potentially by a B-cell depletion and so forth.

It’s not a benign thing to say it’s no big deal. I think that has to go into the consideration in terms of a lack of a significant fraction of patients who were having durable long-term responses, plus infection risks, balanced by the fact that, yes, there are some people who do have durable responses, so therefore we should discuss it with patients. And like Ralph, when you were discussing the guidelines earlier, the ASH guidelines from 2019 say to consider rituximab before splenectomy, which I would also personally agree with, that I would consider rituximab prior to splenectomy. But just understanding that the data have matured to this degree, fortunately, so we really understand the risk and benefit now long term.

Ivy Altomare, MD: Yes. Jim Bussel, MD, is a final author on a recent analysis looking at which patients achieved the best outcomes, so really long-term responders. And in that paper it seemed as though the defined population are women of child-bearing age who have ITP [immune thrombocytopenic purpura] with a diseased duration of less than 2 years, and that is the clinical cohort that gets the longest long-term remissions. The ones that the doctors say, “Well, I get great responses with rituximab. I have a patient who’s 5 years out.” Probably a young woman of childbearing age who was early into her ITP journey. So there are some very good long-term responses, if you use it for the right person.

Richard F. McDonough, MD: Yes, that’s a good point. These epidemiological kind of connections or trends are fascinating to me, because why does it really happen? It’s not maybe exactly clear but at least it helps us clinically to say, “Well, you have a young patient, a healthy woman, perhaps that patient is a little bit of a better candidate than somebody who’s age 85 and has various comorbidities, etcetera, in terms of reaction risk, infection risk, compared to the young, healthy individual.”

Ivy Altomare, MD: Certainly, and now that there are all these other options, it helps to fine-tune treatment.

Terry B. Gernsheimer, MD: And, Ivy, what’s actually interesting about that I think—I haven’t done a splenectomy or asked to have a splenectomy done on a patient in years. But what’s interesting about those data, about rituximab working best in young women who’ve had the disease less than 2 years, those are the same patients who respond to splenectomy long term. So there’s some connection there with that type of patient.

Ivy Altomare, MD: Do you think we could do a randomized study?

Terry B. Gernsheimer, MD: I think we should.

Ivy Altomare, MD: I don’t know. Terry, I want you to talk about platelet transfusion use. Because I know this is an area of interest, and I want to make sure we hit it.

Terry B. Gernsheimer, MD: Yes. And I think it’s very important. I think everyone learns that patients with ITP do not respond to transfusions, to platelet transfusion. And it’s actually not really true. When we did platelet survival studies way back when, what we found is that indeed patients do respond to platelet transfusion, but the response is very short-lived. Those platelets survive for a much shorter time, probably on the 8-hour, several-hour range; whereas their own platelets probably survive 2 to 3 days.

But there is the patient who does require transfusion. If you have a patient who’s in the hospital, who is bleeding, there is no reason not to transfuse them, and in fact, a transfusion may be lifesaving. What’s interesting is that if you transfuse after IVIg [intravenous immunoglobulin therapy], you may actually get a better response. It doesn’t mean that you should wait to give them platelets if they’ve got a CNS [central nervous system] bleeding, for example, or a very severe bleed, until they get the IVIg in because obviously that can take hours. But I would repeat it after the IVIg, hoping that perhaps you get a better response. But it should not be totally avoided.

Ivy Altomare, MD: That’s great guidance.

Amit Mehta, MD: And I think another corollary to that is that we have to keep in mind that even though we think of it as a chronic condition, we have many treatment options nowadays. But there is a small fraction of patients who can even have an intracranial hemorrhage occurrence, or a severe non-intracranial bleed, extra cranial bleeding situation, and if I remember correctly, the fatal intracranial hemorrhage rate is roughly about 0.3% or 0.4% approximately. We’ve always got to bear these kind of worse-case scenarios in our mind and, therefore, especially for an inpatient, it could be indeed lifesaving because of the potential for something like an intracranial hemorrhage.

Transcript Edited for Clarity