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Immunosuppressive Therapy in ITP

Panelists: Ivy Altomare, MD, Duke University Medical Center; Terry Gernsheimer, MD, Fred Hutchingson Cancer Research Center; Keith R McCrae, MD, The Cleveland Clinic
Published: Monday, Feb 19, 2018



Transcript: 

Ivy Altomare, MD: Let’s move on to Rituxan (rituximab), our anti-CD20 monoclonal antibody that is used very often in idiopathic thrombocytopenia purpura. It is not FDA approved for the indication, but as Dr. McCrae mentioned earlier, it is used with good efficacy. So, can you describe what the outcomes are with the use of Rituxan in the second-line setting? You mentioned that it is sometimes used upfront in the first-line setting. In practices, I’ve seen patients getting exposed, multiple times, to courses of Rituxan. Can you comment on what you think is evidence supported, and what you do?

Keith R. McCrae, MD: There’s a number of ways Rituxan can be used in ITP. One is what you just alluded to as a second-line agent. Or, perhaps, as a single agent. In that setting, it’s reported to have a response rate of about 60% to 65%. There are complete responses in maybe 20% to 30% of patients.

Ivy Altomare, MD: What duration of response would we would expect?

Keith R. McCrae, MD: That’s highly variable. It does tend to correlate with the responses. If the patient does get a complete response, he or she tends to stay in remission, in my experience―and really in most of the literature―for 6 months, maybe 9 months, maybe a year, or maybe even longer. If you look at a retrospective study by Patel many years ago, they reported that 20% to 25% of patients had remained in that complete response for 1 year, and maintained that response for 5 years.
That data has been criticized. There are some other studies that have looked at the use of rituximab earlier in the course of disease, often with high-dose steroids, or often with a third immunosuppressive agent for a fixed duration of time. In the right type of patient, primarily a woman with ITP of less than 18 to 24 months’ duration, long-term response rates as high as 60% were reported.

Ivy Altomare, MD: OK. So, early in the course of the disease, in a younger patient?

Keith R. McCrae, MD: Early in the course of disease, in a younger patient. Well, not a younger patient, but females, particularly, seem to do better than males. Again, that data hasn’t been reproduced, and it needs to be. It needs to be studied in more of a randomized manner, as do some of the other reports with a TPO agent. But I think that it tells us that whether it’s rituximab or something else, there may be ways. I’ve always looked at treating ITP kind of like cancer. There are more and more agents now. But at least in the older days when you treated cancer, and I think it’s still largely true, your best chance to treat cancer is right in the beginning.

Ivy Altomare, MD: Yes.

Keith R. McCrae, MD: That’s why people like Sidney Farber and everybody else went back, all these years, mixing combinations of things. They’re different. They treated patients hard, and lo and behold, they finally actually cured some people. And ITP is, I guess, an oligoclonal disease. But I think there’s some evidence and rationale, when you look back in the literature for evolution of ITP clones over the years, for these to become more and more refractory to therapies. Of course, we have more and more therapies, too. So, I think there may be a place for rituximab, up-front, early in the course. There may be a place for TPO agents, as well. Maybe they’re even better. I don’t know. But you can re-treat, if you use it as a standard second-line therapy, particularly in patients who respond well. You can get a reasonable lengthy response. And you can often repeat it. They can get a response that’s just about as long, in my experience.

Ivy Altomare, MD: So, reasonably lengthy would be what?

Keith R. McCrae, MD: Six months, 9 months, or maybe 12 months. If they’re at 200, they may start drifting down at 5 months or 6 months. But they may not need re-treatment for 9 to 12 months. Then, they can get re-treatment, and they might do well for another 9 to 12 months.

Ivy Altomare, MD: So, you find it reasonable to give a second course of Rituxan, upon relapse, if the duration has been 6 to 9 months? After that second course of Rituxan, if you get a shorter duration of response, is it reasonable to re-treat again? How do you gauge what to do after the second course?

Keith R. McCrae, MD: Well, if their responses are getting shorter and shorter, you sit down and have a talk with the patient. You say, “You know, this basically allowed you to go for maybe 2 years and not have to take medication every day or every week. You lived a normal life, taking no medicines, and were quite happy. We got some mileage out of that. We have diminishing returns now, so it’s probably time to think about other things.”

Ivy Altomare, MD: What risks are there to Rituxan in this really benign disease? What do you talk with the patients about?

Keith R. McCrae, MD: My opinion and experience is that rituximab is actually quite safe. Of course, there is the first infusion reaction that everyone knows about. I think that’s uncommon, and even less common if you premedicate with steroids and things. But that’s something you do have to deal with. I’ve had a couple patients who have had serum sickness with rituximab, which was really unusual. But that’s something to be aware of. It is an immunosuppressive drug. If you look carefully, there’s probably a slight increase in infections in these patients. Everybody talks about PML (progressive multifocal leukoencephalopathy). There has been 1 case, maybe 2 cases, of PML in patients who have received rituximab along with all kinds of immunosuppressives, and steroids, and everything for years and years, who had lupus. So, there is a theoretical risk of PML with rituximab, but I don’t think that’s something of major concern.

Transcript Edited for Clarity 

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Transcript: 

Ivy Altomare, MD: Let’s move on to Rituxan (rituximab), our anti-CD20 monoclonal antibody that is used very often in idiopathic thrombocytopenia purpura. It is not FDA approved for the indication, but as Dr. McCrae mentioned earlier, it is used with good efficacy. So, can you describe what the outcomes are with the use of Rituxan in the second-line setting? You mentioned that it is sometimes used upfront in the first-line setting. In practices, I’ve seen patients getting exposed, multiple times, to courses of Rituxan. Can you comment on what you think is evidence supported, and what you do?

Keith R. McCrae, MD: There’s a number of ways Rituxan can be used in ITP. One is what you just alluded to as a second-line agent. Or, perhaps, as a single agent. In that setting, it’s reported to have a response rate of about 60% to 65%. There are complete responses in maybe 20% to 30% of patients.

Ivy Altomare, MD: What duration of response would we would expect?

Keith R. McCrae, MD: That’s highly variable. It does tend to correlate with the responses. If the patient does get a complete response, he or she tends to stay in remission, in my experience―and really in most of the literature―for 6 months, maybe 9 months, maybe a year, or maybe even longer. If you look at a retrospective study by Patel many years ago, they reported that 20% to 25% of patients had remained in that complete response for 1 year, and maintained that response for 5 years.
That data has been criticized. There are some other studies that have looked at the use of rituximab earlier in the course of disease, often with high-dose steroids, or often with a third immunosuppressive agent for a fixed duration of time. In the right type of patient, primarily a woman with ITP of less than 18 to 24 months’ duration, long-term response rates as high as 60% were reported.

Ivy Altomare, MD: OK. So, early in the course of the disease, in a younger patient?

Keith R. McCrae, MD: Early in the course of disease, in a younger patient. Well, not a younger patient, but females, particularly, seem to do better than males. Again, that data hasn’t been reproduced, and it needs to be. It needs to be studied in more of a randomized manner, as do some of the other reports with a TPO agent. But I think that it tells us that whether it’s rituximab or something else, there may be ways. I’ve always looked at treating ITP kind of like cancer. There are more and more agents now. But at least in the older days when you treated cancer, and I think it’s still largely true, your best chance to treat cancer is right in the beginning.

Ivy Altomare, MD: Yes.

Keith R. McCrae, MD: That’s why people like Sidney Farber and everybody else went back, all these years, mixing combinations of things. They’re different. They treated patients hard, and lo and behold, they finally actually cured some people. And ITP is, I guess, an oligoclonal disease. But I think there’s some evidence and rationale, when you look back in the literature for evolution of ITP clones over the years, for these to become more and more refractory to therapies. Of course, we have more and more therapies, too. So, I think there may be a place for rituximab, up-front, early in the course. There may be a place for TPO agents, as well. Maybe they’re even better. I don’t know. But you can re-treat, if you use it as a standard second-line therapy, particularly in patients who respond well. You can get a reasonable lengthy response. And you can often repeat it. They can get a response that’s just about as long, in my experience.

Ivy Altomare, MD: So, reasonably lengthy would be what?

Keith R. McCrae, MD: Six months, 9 months, or maybe 12 months. If they’re at 200, they may start drifting down at 5 months or 6 months. But they may not need re-treatment for 9 to 12 months. Then, they can get re-treatment, and they might do well for another 9 to 12 months.

Ivy Altomare, MD: So, you find it reasonable to give a second course of Rituxan, upon relapse, if the duration has been 6 to 9 months? After that second course of Rituxan, if you get a shorter duration of response, is it reasonable to re-treat again? How do you gauge what to do after the second course?

Keith R. McCrae, MD: Well, if their responses are getting shorter and shorter, you sit down and have a talk with the patient. You say, “You know, this basically allowed you to go for maybe 2 years and not have to take medication every day or every week. You lived a normal life, taking no medicines, and were quite happy. We got some mileage out of that. We have diminishing returns now, so it’s probably time to think about other things.”

Ivy Altomare, MD: What risks are there to Rituxan in this really benign disease? What do you talk with the patients about?

Keith R. McCrae, MD: My opinion and experience is that rituximab is actually quite safe. Of course, there is the first infusion reaction that everyone knows about. I think that’s uncommon, and even less common if you premedicate with steroids and things. But that’s something you do have to deal with. I’ve had a couple patients who have had serum sickness with rituximab, which was really unusual. But that’s something to be aware of. It is an immunosuppressive drug. If you look carefully, there’s probably a slight increase in infections in these patients. Everybody talks about PML (progressive multifocal leukoencephalopathy). There has been 1 case, maybe 2 cases, of PML in patients who have received rituximab along with all kinds of immunosuppressives, and steroids, and everything for years and years, who had lupus. So, there is a theoretical risk of PML with rituximab, but I don’t think that’s something of major concern.

Transcript Edited for Clarity 
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