Focusing on second-line systemic agents in immune thrombocytopenia, experts review the historical use of rituximab therapy.
Morey Blinder, MD: Let’s move off splenectomy and move on to rituximab, another therapy that’s been around for more than 20 years, probably closer to 30 years, for ITP [immune thrombocytopenia]. I’d like to think about it in the COVID-19 era. Has that changed anybody’s approach to how frequently or where in the lineup we use rituximab? I was very concerned early on in COVID-19, and then my concerns lessened a little. In the understanding of the vaccine modulation or attenuation, I’m worried about it again. Howard, what are your thoughts about rituximab? Where does that fit in with its mechanism of action in the COVID-19 era, which we’re in pretty firmly?
Howard Liebman, MD: I agree with you. It’s made us rethink the issue. But even before COVID-19, we were changing our patterns based on a paper by Jim Bussel’s group about the responders. We knew in the paper by [Anil] Patel that it was only going to be 20% at 5 years and 30% at 2 years. Who was it? Jim showed it. It was supported by another paper from Italy. Another cohort found it was predominantly women in the childbearing years in the first couple of years of the disease. For that reason, we made that an option for younger women, but we favored older patients and men, mentioning thrombopoietin-receptor agonist as an option.
We add on the issue of COVID-19 and the failure to have immunization. Even though we have very good therapeutics for the patients who have to be hospitalized, people are still dying of COVID-19. We encourage immunization. We can talk about the adverse effects of immunization because we have recently published in Blood the outcomes of immunization in ITP adults. We use it less, but we still consider it, and we’ll take it to patients who’ve been immunized.
We have to keep building and measuring their spike protein response. If they had a positive spike protein response, we might use it in a difficult patient afterward in the hope that we can obtain remission. We can wait for the recovery of their host immune system, which is usually within 6 months based on Don Arnold’s experience and our experience as a single-dose issue. Then we can immunize and boost them again.
Morey Blinder, MD: I have a lot of Rituxan thoughts related to what era you were in. Earlier, I thought of it as a steroid-sparing therapy. If you had somebody on longer-term steroids, even if your response rates weren’t great, and the long-term response rates were less good, it was a way to get some people off or to decrease steroid usage. With more therapies, that argument is less. The COVID-19 era makes it less. Cindy, are there many roles for rituximab in the pediatric population?
Cindy Neunert, MD: To the point about young women and childbearing-age women, I tend to think about rituximab a little more in my adolescent female population. That’s definitely the group where it may have a role. We’ve also become quite concerned in the pediatric arena about some children developing persistent hypergammaglobulinemia following rituximab use. We need to better understand that a lot of people are becoming reluctant to use rituximab, particularly in very young and developing immune systems. [We don’t know if] these are children who we’re going to develop to a CVID [common variable immunodeficiency]–like picture at some point anyway, and the rituximab just moves it along and uncovers it.
There’s some work being done out of the group in Atlanta—immunology as well as hematology—looking at biomarkers for uncovering those patients who will be more at risk in terms of their immunoglobulin and TMB [tumor mutational burden] cell panels going into rituximab therapy. Also, we have the luxury of having really large gene screens that we can do looking for underlying primary immune deficiencies. It seems that those are the children more at risk, or the ones that have a signal. We don’t screen everybody. Until we get a little more integrated in our clinical practice with what we know on the research side, people are reluctant to use rituximab in the pediatric population, but I use it more. I reserve it more for adolescent women. I’ve seen good responses in that population.
Morey Blinder, MD: That’s a really interesting perspective. Thank you. Danny, do you want to say anything more about rituximab?
Daniel Landau, MD: The big message that I discuss with a lot of my patients is exactly what Howard mentioned, that the long-term response rates are not ideal. Some papers speak to this law of diminishing returns: if you’re going to try Rituxan again in relatively short order, it’s not going to work very well. We’re still tied to Rituxan in the lymphoma world. There’s no choice there. But in a disease state with other options, I prefer to avoid excessive exposure to rituximab in the COVID-19 era. Also, a number of patients haven’t been excited about having to come to the infusion center for various reasons, COVID-19 included. Therapies that allow them to be dosed at home instead of inside the hospital have been preferential.
Morey Blinder, MD: That’s another point worth making about coming in relatively often to do that. Those are all good points related to rituximab, and the landscape shifts all the time.
Transcript edited for clarity.