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Rituximab and Salvage Therapies for Patients With ITP

Panelists: Ivy Altomare, MD, Duke University Medical Center; Ralph V. Boccia, MD, FACP, LLC, Georgetown University Medical Center; Amit Mehta, MD Independent Hematology and Oncology Practice
Published: Wednesday, Feb 20, 2019



Transcript: 

Ivy Altomare, MD: What about rituximab? Are you using rituximab these days for ITP [immune thrombocytopenia purpura]?

Ralph V. Boccia, MD, FACP, LLC: I do. I tend to use it more often in a patient who has another autoimmune disorder, because I really think you get the dual effect then if you have it. And I think those are the patients who respond the best to rituximab. If you look at the data, the data are no better really than corticosteroids. It’s really the 20%, 25%, maybe 30% when you use it with dexamethasone that has a sustained response. Otherwise, you’re going to be revisiting the well again and asking yourself if you want to do it again or if you want to move on to something else in the vast majority of patients. I think it’s a very good drug. The nice thing about it compared with the other agents is it’s done in 4 weeks, as opposed to continuing the oral or continuing the parenteral, so in that sense, I do like it. But you have the downside risk of reactivating hepatitis B or the downside risk of the B-cell immunosuppression that you get, although we don’t see a whole lot from that. But this is a more often younger population, and we don’t know 30 years from now what that patient is going to be like in a benign disease opposed to a malignant disease.

Ivy Altomare, MD: Exactly. I absolutely agree. I think that it’s really difficult to determine the real long-term risk of the immunosuppression. And in the ITP space, any series is going to be complicated by the fact that these patients get subsequent immunosuppression with other agents. So it’s going to be really hard to determine, but I think that in trying to preserve the immune system, the good part of the immune system in these patients is, I think, important.

Amit Mehta, MD: The other thing with rituximab is that it’s a fixed duration for weekly rituximab infusion. So that may be appealing for some patients where they say, OK, a fixed duration, and I’ll see what kind of response I get from the medication if I do have any kind of lasting durable response, as opposed to if they’re started on any of the medication—whether you talk about fostamatinib, eltrombopag, romiplostim—they’re basically consigned to, besides the few people where we might stop selectively. But on the whole, they’re continuing indefinitely, so that may be appealing to some people. And the ASH [American Society of Hematology] guidelines commented on the ASH authors, I guess, and they said that from a cost perspective, that is something to consider in today’s world of healthcare economics and so forth.

Ivy Altomare, MD: That is true.

Amit Mehta, MD: Not that rituximab is cheap, but when you say 4 versus monthly ongoing, there is a cost difference as well.

Ivy Altomare, MD: So I have seen fewer consults for second opinions for patients who have been treated extensively with several courses of Rituxan. I do think that years ago we would see that often, right? ITP patients would get a course of rituximab and then have a response, and then upon relapse get another course of rituximab. And then the duration of response is typically shorter and shorter. So I don’t think that that’s really an effective strategy, but my question is, when would you do that? Is there a case where you would treat with Rituxan and then consider retreating?

Amit Mehta, MD: Yeah. It’s a great point. So I think in general, the studies have shown, as you alluded to nicely, that the retreatment has diminishing returns with rituximab. So it can be considered, especially before we had newer agents as we do today, it could be considered. But there are diminishing returns. I believe the studies have shown—the most recent one I saw was about a 10% ongoing response rate for retreated rituximab patients, 2 or more retreatments. So that’s 1 factor. Now, the patient for whom I may consider it, that all being said, so I had a patient I can talk about who came to my clinic, and he had a very robust response to rituximab about 8 years ago that I happened to have treated. And he kind of fell off the radar because he was doing great. His platelet count was over, like, 200,000, and then he was re-referred to me just earlier this year, January, February-ish, and he had a platelet count that was less than 10,000, like 6000 or 7000.

Ivy Altomare, MD: And it’s 8 years later.

Amit Mehta, MD: Eight years later. He talked to me about this. I said, well, we have many more options now than we did 8 or 9 years ago, whenever he exactly was treated. And so he asked me about whether I should retreat rituximab. And so that was a patient where I did wind up doing it, even though normally I don’t. But that is a patient who I did retreat with rituximab because it had been so long and he responded so well. And incidentally, this patient again responded well. So it’s just 1 of those things. I mean, it’s been only a few months so we’ll see how durable the response is.

Ivy Altomare, MD: Even if he gets 4 years now.

Amit Mehta, MD: If he gets 4 years, he’ll be happy.

Ivy Altomare, MD: Yeah, exactly.

Amit Mehta, MD: The other thing I always wonder with these patients is whether there was some trigger. I have seen it where it was like a relapse. I have seen it where somebody was rock stable, and then they got some kind of bad viral infection, pneumonia, or something that might have set it off again, so to speak. Because this particular patient, he just happened to have developed, about like a month and a half, 2 months after he got a pneumonia that he was hospitalized for around December of last year. It’s hypothetical in a way, but I wonder if that kind of somehow changed his immune balance, the T cell, T-regulator cell depression, who knows. But something happened that I think caused that to trigger. What went through my mind is does he have some kind of low-level autoantibodies present in his circulation the whole time, and they kind of maybe got stimulated by this process. But that’s a patient for whom I do that I very selectively. But on the whole, I don’t do that, I don’t retreat with rituximab because, as you said earlier, there are poor response rates with a shorter duration.

Ivy Altomare, MD: And the long-term risk probably of immunosuppression. You mentioned a patient who had a very robust and durable response. So what about the patients who are refractory to everything? What about the patients who have gotten all of these therapies, and I’m using this example to lead into when you use the other immunosuppressants like cyclosporine or MMF [mycophenolate mofetil].

Ralph V. Boccia, MD, FACP, LLC: There are some people, as we mentioned at the very beginning—since it’s a heterogeneous disease—those with around 5000 platelets, I’m sure you have them in your clinic, who don’t even have petechiae.

Ivy Altomare, MD: Yeah.

Ralph V. Boccia, MD, FACP, LLC: And so you were treating the number before and not the patient. So there are some people I will just say, OK, you’re at risk for bleeding, but you know you haven’t been bleeding, and you apparently have reasonable coagulation because you’re not developing mucosal or cutaneous evidence for doing it, then I’ll just leave them off it. But on the other hand, then you have somebody who has constant nosebleeds, a woman with heavy menstrual periods, somebody who’s got urinary tract bleeding and whatnot, and then you just have to look for something else. And that something else can be cyclosporine, can be cyclophosphamide, can be azathioprine.

Ivy Altomare, MD: We’ve all used it.

Ralph V. Boccia, MD, FACP, LLC: Can be Danazol. They all have downside risks, and we know that. I mean, secondary malignancies, those we’ve seen also, mycophenolate. So lots of other options, none of which are very good at that point in time. Response rates are in the 10% range for anything else you choose at that point. Bone marrow transplant—that’s been done obviously for ITP as well.

Ivy Altomare, MD: It sounds scary.

Ralph V. Boccia, MD, FACP, LLC: It is very scary.

Ivy Altomare, MD: Yeah, I’ve never done that.

Ralph V. Boccia, MD, FACP, LLC: I haven’t either.

Ivy Altomare, MD: If I have a patient, I’ll send them to you.

Ralph V. Boccia, MD, FACP, LLC: All right.

Amit Mehta, MD: Also, the timing of the response for those later-line agents is very slow.

Ivy Altomare, MD: Excellent point, absolutely.

Amit Mehta, MD: If the patient does need acute stabilization of hemostasis being achieved and so forth, that becomes a practical issue. I’ve used these kinds of drugs occasionally, especially in years past, and it often takes, like, a few months to get a response. It takes a few months.

Ivy Altomare, MD: And when you’re in dire straits, the patient is refractory to everything, and then we pull these out, and we’ve got to wait 5 weeks for a response. It’s very worthwhile knowing.

Amit Mehta, MD: Yeah, and I think as Ralph said earlier, at that point really you just have to pull out all the stops and hope that giving them IVIG [intravenous immunoglobin], giving them steroids retreatment, giving them platelet transfusion if there is a clinical bleeding concern going on. And then what do you do long term? Who knows, but stabilize the patient first, and then hope that some of these other…

Ivy Altomare, MD: You just cross your fingers.

Amit Mehta, MD: Cross your fingers that later-line agents will work.

Ralph V. Boccia, MD, FACP, LLC: Do you use high-dose cyclophosphamide?

Ivy Altomare, MD: Not for ITP.

Transcript Edited for Clarity

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Transcript: 

Ivy Altomare, MD: What about rituximab? Are you using rituximab these days for ITP [immune thrombocytopenia purpura]?

Ralph V. Boccia, MD, FACP, LLC: I do. I tend to use it more often in a patient who has another autoimmune disorder, because I really think you get the dual effect then if you have it. And I think those are the patients who respond the best to rituximab. If you look at the data, the data are no better really than corticosteroids. It’s really the 20%, 25%, maybe 30% when you use it with dexamethasone that has a sustained response. Otherwise, you’re going to be revisiting the well again and asking yourself if you want to do it again or if you want to move on to something else in the vast majority of patients. I think it’s a very good drug. The nice thing about it compared with the other agents is it’s done in 4 weeks, as opposed to continuing the oral or continuing the parenteral, so in that sense, I do like it. But you have the downside risk of reactivating hepatitis B or the downside risk of the B-cell immunosuppression that you get, although we don’t see a whole lot from that. But this is a more often younger population, and we don’t know 30 years from now what that patient is going to be like in a benign disease opposed to a malignant disease.

Ivy Altomare, MD: Exactly. I absolutely agree. I think that it’s really difficult to determine the real long-term risk of the immunosuppression. And in the ITP space, any series is going to be complicated by the fact that these patients get subsequent immunosuppression with other agents. So it’s going to be really hard to determine, but I think that in trying to preserve the immune system, the good part of the immune system in these patients is, I think, important.

Amit Mehta, MD: The other thing with rituximab is that it’s a fixed duration for weekly rituximab infusion. So that may be appealing for some patients where they say, OK, a fixed duration, and I’ll see what kind of response I get from the medication if I do have any kind of lasting durable response, as opposed to if they’re started on any of the medication—whether you talk about fostamatinib, eltrombopag, romiplostim—they’re basically consigned to, besides the few people where we might stop selectively. But on the whole, they’re continuing indefinitely, so that may be appealing to some people. And the ASH [American Society of Hematology] guidelines commented on the ASH authors, I guess, and they said that from a cost perspective, that is something to consider in today’s world of healthcare economics and so forth.

Ivy Altomare, MD: That is true.

Amit Mehta, MD: Not that rituximab is cheap, but when you say 4 versus monthly ongoing, there is a cost difference as well.

Ivy Altomare, MD: So I have seen fewer consults for second opinions for patients who have been treated extensively with several courses of Rituxan. I do think that years ago we would see that often, right? ITP patients would get a course of rituximab and then have a response, and then upon relapse get another course of rituximab. And then the duration of response is typically shorter and shorter. So I don’t think that that’s really an effective strategy, but my question is, when would you do that? Is there a case where you would treat with Rituxan and then consider retreating?

Amit Mehta, MD: Yeah. It’s a great point. So I think in general, the studies have shown, as you alluded to nicely, that the retreatment has diminishing returns with rituximab. So it can be considered, especially before we had newer agents as we do today, it could be considered. But there are diminishing returns. I believe the studies have shown—the most recent one I saw was about a 10% ongoing response rate for retreated rituximab patients, 2 or more retreatments. So that’s 1 factor. Now, the patient for whom I may consider it, that all being said, so I had a patient I can talk about who came to my clinic, and he had a very robust response to rituximab about 8 years ago that I happened to have treated. And he kind of fell off the radar because he was doing great. His platelet count was over, like, 200,000, and then he was re-referred to me just earlier this year, January, February-ish, and he had a platelet count that was less than 10,000, like 6000 or 7000.

Ivy Altomare, MD: And it’s 8 years later.

Amit Mehta, MD: Eight years later. He talked to me about this. I said, well, we have many more options now than we did 8 or 9 years ago, whenever he exactly was treated. And so he asked me about whether I should retreat rituximab. And so that was a patient where I did wind up doing it, even though normally I don’t. But that is a patient who I did retreat with rituximab because it had been so long and he responded so well. And incidentally, this patient again responded well. So it’s just 1 of those things. I mean, it’s been only a few months so we’ll see how durable the response is.

Ivy Altomare, MD: Even if he gets 4 years now.

Amit Mehta, MD: If he gets 4 years, he’ll be happy.

Ivy Altomare, MD: Yeah, exactly.

Amit Mehta, MD: The other thing I always wonder with these patients is whether there was some trigger. I have seen it where it was like a relapse. I have seen it where somebody was rock stable, and then they got some kind of bad viral infection, pneumonia, or something that might have set it off again, so to speak. Because this particular patient, he just happened to have developed, about like a month and a half, 2 months after he got a pneumonia that he was hospitalized for around December of last year. It’s hypothetical in a way, but I wonder if that kind of somehow changed his immune balance, the T cell, T-regulator cell depression, who knows. But something happened that I think caused that to trigger. What went through my mind is does he have some kind of low-level autoantibodies present in his circulation the whole time, and they kind of maybe got stimulated by this process. But that’s a patient for whom I do that I very selectively. But on the whole, I don’t do that, I don’t retreat with rituximab because, as you said earlier, there are poor response rates with a shorter duration.

Ivy Altomare, MD: And the long-term risk probably of immunosuppression. You mentioned a patient who had a very robust and durable response. So what about the patients who are refractory to everything? What about the patients who have gotten all of these therapies, and I’m using this example to lead into when you use the other immunosuppressants like cyclosporine or MMF [mycophenolate mofetil].

Ralph V. Boccia, MD, FACP, LLC: There are some people, as we mentioned at the very beginning—since it’s a heterogeneous disease—those with around 5000 platelets, I’m sure you have them in your clinic, who don’t even have petechiae.

Ivy Altomare, MD: Yeah.

Ralph V. Boccia, MD, FACP, LLC: And so you were treating the number before and not the patient. So there are some people I will just say, OK, you’re at risk for bleeding, but you know you haven’t been bleeding, and you apparently have reasonable coagulation because you’re not developing mucosal or cutaneous evidence for doing it, then I’ll just leave them off it. But on the other hand, then you have somebody who has constant nosebleeds, a woman with heavy menstrual periods, somebody who’s got urinary tract bleeding and whatnot, and then you just have to look for something else. And that something else can be cyclosporine, can be cyclophosphamide, can be azathioprine.

Ivy Altomare, MD: We’ve all used it.

Ralph V. Boccia, MD, FACP, LLC: Can be Danazol. They all have downside risks, and we know that. I mean, secondary malignancies, those we’ve seen also, mycophenolate. So lots of other options, none of which are very good at that point in time. Response rates are in the 10% range for anything else you choose at that point. Bone marrow transplant—that’s been done obviously for ITP as well.

Ivy Altomare, MD: It sounds scary.

Ralph V. Boccia, MD, FACP, LLC: It is very scary.

Ivy Altomare, MD: Yeah, I’ve never done that.

Ralph V. Boccia, MD, FACP, LLC: I haven’t either.

Ivy Altomare, MD: If I have a patient, I’ll send them to you.

Ralph V. Boccia, MD, FACP, LLC: All right.

Amit Mehta, MD: Also, the timing of the response for those later-line agents is very slow.

Ivy Altomare, MD: Excellent point, absolutely.

Amit Mehta, MD: If the patient does need acute stabilization of hemostasis being achieved and so forth, that becomes a practical issue. I’ve used these kinds of drugs occasionally, especially in years past, and it often takes, like, a few months to get a response. It takes a few months.

Ivy Altomare, MD: And when you’re in dire straits, the patient is refractory to everything, and then we pull these out, and we’ve got to wait 5 weeks for a response. It’s very worthwhile knowing.

Amit Mehta, MD: Yeah, and I think as Ralph said earlier, at that point really you just have to pull out all the stops and hope that giving them IVIG [intravenous immunoglobin], giving them steroids retreatment, giving them platelet transfusion if there is a clinical bleeding concern going on. And then what do you do long term? Who knows, but stabilize the patient first, and then hope that some of these other…

Ivy Altomare, MD: You just cross your fingers.

Amit Mehta, MD: Cross your fingers that later-line agents will work.

Ralph V. Boccia, MD, FACP, LLC: Do you use high-dose cyclophosphamide?

Ivy Altomare, MD: Not for ITP.

Transcript Edited for Clarity
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