During a Case-Based Roundtable® event, Michael R. Bishop, MD, moderated a discussion on monitoring and treatment of chronic graft-vs-host disease.
EVENT REGION Great Lakes
PARTICIPANT LIST Neel Shah, MD | Jose Paredes, MD | Rachel Phelan, MD | William Tse, MD
Bishop: I would be interested to know how much [nontransplant physicians] are involved in that posttransplant follow-up. [Do] any of you want to share your approach or method toward chronic GVHD monitoring, assessment, and scoring,…or do you primarily rely on your transplant center for this?
Shah: I think for the transplanters, I would assume that they would take responsibility for following these patients locally. I have some patients with GVHD whom I follow with the transplanter. I expect it to be a team effort, not necessarily one or the other managing [the patient]. Obviously, initially [we use] steroids and try to taper that. But I’d still want the transplanter to see the patient probably once a month and just make sure that things are going in the right direction.
Bishop: Yes, and I hope…what’s happening with all of you is that your transplant center is working closely with you. For some patients, getting them to come back to the transplant center is often difficult. Sometimes they even refuse to, and sometimes it’s just not possible due to social or physical barriers. So the nontransplanter’s involvement is essential in doing this.
Paredes: [I have] very little experience. We don’t see those patients, and normally they stay where they [received the] transplant. It’s very interesting to hear how to handle them….
Bishop: I’m glad you’re sharing that. I think the joint collaboration between the referring physicians and the transplant center is imperative. It’s something I’ve tried to always push forward….
To follow this up, if you have a patient who you think is an appropriate transplant candidate, do you talk to your patients about the risk of both acute and chronic GVHD? I’d be interested to hear [about that] because the first thing they read about [online] is GVHD. It’s the most common question I get when I have a patient coming in to see me. I’d be interested to hear how you counsel your patients regarding that.
Shah: I have a new patient with therapy-related myelodysplastic syndrome [MDS], and I had a couple of patients with AML whom I referred [for transplant]. We talk a little bit about allogeneic vs autologous [transplant] and what that means. But ultimately, [when] I’m referring them in a situation for allogeneic [transplant], they’re either going to die or they’re going to get the transplant. There aren’t very good options for them, so most patients are willing to take that risk when you’re talking about a terminal disease like AML.
Bishop: That’s a great point because it is a balance of risk and benefits. I know I have a bias, but that’s why I went into transplantation: trying to help those patients. Just to put it in perspective, there are about 40,000 allogeneic [hematopoietic stem cell] transplants performed in the United States every year. A great example of that is therapy-related MDS, which is almost [always] fatal without an allogeneic transplant. But despite chimeric antigen receptor T cells and autologous transplant, there’s still a large proportion of patients still undergoing allogeneic [hematopoietic] stem cell transplantation.
DISCUSSION QUESTIONS
Bishop: Considering the REACH3 data, does it impact your perception of ruxolitinib for chronic GVHD? Relative to that, did anything stand out in terms of efficacy and safety data relative to ruxolitinib for steroid-refractory chronic GVHD?
Phelan: I’m a transplanter, so I use ruxolitinib and I’m familiar with it and I like using it. What I maybe didn’t fully realize before is the complete response [CR] vs partial responses, where the CR rate is quite small if you look at the percentage [From the Data].1 Many patients respond but don’t have a CR, so I think that’s important to know in terms of expectations. That’s probably also where patient-reported outcome data are also important because having a CR might not be necessary for an improved quality of life.
Bishop: That’s a fantastic point. It is [about] managing those expectations. It’s hard to get a [CR], especially when you have steroid-refractory chronic GVHD, and we know that most of those participating on this [trial] had moderate to severe [GVHD]. They had multiple organ involvement, and yet you can have an improvement in one organ and not necessarily in another, so getting those CRs is tough. I think that’s a good point. Like you said, setting expectations and what to expect is very important.
DISCUSSION QUESTIONS
Bishop: There are multiple options for chronic GVHD. Extracorporeal photopheresis [ECP], rituximab [Rituxan], and ibrutinib [Imbruvica] still have a role. [In terms of] the factors that may impact your choice, I think steroid-refractory disease and steroid-dependent disease definitely do [factor into] where you’re going to implement [the therapy]. It may be the severity of the disease, but there are also patient factors that affect [your choice]. We’re sometimes hesitant in patients who have poor [blood cell] counts; often thrombocytopenia is a manifestation of chronic GVHD. There is hesitancy in starting ruxolitinib in a patient with low counts.
Thinking about some of the AE [adverse event] profiles and what other problems the patient has,…often [patients] need insurance approval before you can start [treatment], even though most if not all of these drugs have excellent patient support. It used to be if you even wanted to get started on them, you couldn’t, even though… the earlier you start, the better. But now they have programs so they at least will provide you with the drug until you get insurance approval. That becomes a very important thing.
The final thing is we’ve already had some [experience with] combination use. The goal is to get them off steroids and using a combination of the drugs in order to do that.
Tse: I have a comment about one of the trials…the [phase 3 iNTEGRATE trial (NCT02959944) of the] combination of up-front steroids and ibrutinib. I don’t think this trial is necessarily a failure from my perspective. We could probably have a better design than this trial because, in my experience, I also commonly use the combination. But in those patients, the combination [enabled patients to] much more successfully and [rapidly] taper off the steroid. These trials should be designed to tell whether ibrutinib plus a steroid can be tapered off faster and better, and that would be a positive trial.
Bishop: I would agree with that because the steroid complications are extensive and problematic. That’s a very good point.
Paredes: Is there any problem with using one before the other? Let’s say ruxolitinib ahead of belumosudil [Rezurock] or the opposite?
Bishop: Based upon the trial that [led to approval of] belumosudil, patients had to have either [prior] ibrutinib or ruxolitinib. The indication is for those patients who have already received [2 prior lines, such as] ruxolitinib, and so it’s hard to get it approved ahead of time unless you can demonstrate that ruxolitinib is contraindicated.2
Phelan: I’ll just add that I think we use a very similar approach in pediatrics. An added layer of complication is whether [the agent is] available in a liquid format, depending on the patient’s age. And obviously, many of the drugs aren’t FDA approved [for patients younger than 12 years], although we [may] still use them. I don’t know compared with adults, but with ECP, it’s sometimes less complicated because if the patients are young enough, the parents will bring them to their frequent appointments. But we see differences and loss to follow-up and things [like that] when we are dealing with young adults.
Bishop: Yes. With adults, it’s tough [to take the time for ECP]. Having dealt with…children, young adults, and adults, the adults are the most reluctant to receive ECP. It’s disappointing sometimes because we find that that’s a great combination to get them off steroids as well, particularly while they’re on ruxolitinib or belumosudil, so that’s a great point.
I can tell you, I wish I could get more of the suspension for my patients because they hate taking pills, so I’m in agreement with you, particularly when they have horrible esophageal GVHD. I think that’s one of the more debilitating aspects of chronic GVHD.
Tse: ECP was never FDA approved, and even today, we are talking about it. When I am exploring options [with the insurance] company, [I think about] why it continues to survive because there are so many competitive drugs.
Bishop: Yes…I was one of the first people in the United States to use ECP for chronic GVHD.… But you’re exactly right. Trying to get FDA approval was very difficult [based on the studies].
Tse: I was recently talking to [individuals at] a German company and gave them advice because they have a machine [that] can do not only ECP but also can do a plasma exchange. I was telling them when you have ECP plus plasma exchange for the same patient, I think the outcome would be even better.
Bishop: Yes, you might very well be right.
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