Affected Organs and Availability Influence Choice of cGVHD Therapy

In the past years, new and more effective therapies have been introduced to manage chronic graft-vs-host disease (cGVHD). The application of the novel therapies can be complicated and may involve overlapping durations of treatment with steroids and one other. In a recent virtual Case-Based Roundtable meeting, Nelson J. Chao, MD, MBA, Donald D. and Elizabeth G. Cooke Cancer Distinguished Research Professor at Duke University School of Medicine, reviewed trial data and asked participants how these therapies should be given based on their approved indications and aspects such as organ-specific treatment response. With more treatment options available, physicians have the capability to try additional options if steroids and second-line GVHD therapy yields an inadequate response.

This article is part 2 of a 2-part series from a Case-Based Roundtable event.

DISCUSSION QUESTIONS

• Considering the REACH3 (NCT03112603) 3-year data:​
  • Do the data impact your perception of ruxolitinib (Jakafi) for cGVHD?​
  • What stands out from the efficacy and safety data?

Nelson J. Chao, MD: What do you think about the efficacy and the safety data? Do you think your real-world experience mimics this?

Harold M. Chung, MD: I think it does. We've had a lot of success with it, but having the REACH3 data with a crossover [from the control arm] that does just as well was pretty impressive.¹ Our patients can tolerate the ruxolitinib pretty well.

Meilin Diaz-Paez, MSN, ARPN: Yes, we've been able to successfully taper patients off systemic steroids like prednisone and leave them on ruxolitinib once their GVHD have been quite stable. I have successfully tapered patients off ruxolitinib and still maintain them in a quiescent state.

Chung: Out of curiosity, how long do you keep them on the standard dose of ruxolitinib before you start to taper?

Diaz-Paez: It depends how often they can tolerate it, and if we've had any [GVHD] flares on the full treatment dose. If I have patients on full treatment dose with no flare and stable disease, we can start trying to taper them at 3 months. If they do flare, then we might keep them a little bit longer and try to taper within 6 months to 1 year. It depends on how they're tolerating it and how much success we've seen in regression of their symptoms.

Konstantinos Sdrimas, MD: Interesting, because we have good results too, but if people respond, we usually wait 6 months before we start tapering.

Chao: We do very much the same thing. If at the end of 3 months they have a near-complete response, we start to slowly walk them down. You have to remember, ruxolitinib is immunosuppressive. They can get infectious complications, so it's not completely benign.

Diaz-Paez: A lot of these patients are on 2 lines [at once]. They're typically on systemic prednisone, and then you add ruxolitinib, and in my practice, I always like to try to taper. I feel like prednisone is [challenging], so I always try to get them off prednisone, keep them stable on ruxolitinib, and then slowly peel off the ruxolitinib. That's why it might take a little bit longer, because my goal is to always try to get off the prednisone first.

Chao: It's interesting because in my practice with older patients, I very frequently leave them on 5 mg of prednisone, and I think it's homeopathic; it probably treats me more than the patient.

Diaz-Paez: We've had some cases where they had been on it for so long and we pull them off, then we start checking cortisol levels shortly afterwards, and they still need some support. But 5 mg of prednisone every day or every other day is, like you said, [an ineffective dose].

DISCUSSION QUESTIONS

• What is your reaction to the efficacy and safety data of the AGAVE-201 trial (NCT04710576)?
• What is your experience with/perception of axatilimab [Niktimvo] for cGVHD?

Chung: I haven't used the drug, but I haven't seen a lot of patients recently with gastrointestinal [GI] GVHD. It looked pretty promising from the AGAVE-201 study that it works so well for people with GI GVHD.²

Diaz-Paez: We got this on formulary in January or February, and to get it approved is quite challenging. We’ve probably had 2 patients who we put on it in our division, but from my patient group, I have not had any patients with access to the medication yet.

Chao: It is expensive, so we do have to go through our high impact review committee to get patients on it.

Sdrimas: I know that our group tried, and there are many delays because of insurance approval….

Chao: Some of this is because it's new, and I think any new drug will go through some of these machinations as payers get used to it. But it does take a while.

Diaz-Paez: We probably will start seeing some more because our institution is currently taking part in a clinical trial [NCT06663722] where we're having patients with axatilimab and extracorporeal photopheresis for management of their GVHD. It looks like we're starting to [move forward] with this one at our institution.

DISCUSSION QUESTIONS

• What factors impact on your treatment choices for:​
  • Steroid-refractory/-dependent/-intolerant disease?​
  • Mild, moderate, or severe disease?​
• Are there patient-specific factors that influence your decision?​
• What has been your experience with combination use?

Chao: It’s interesting because historically, it was steroids, then it was ruxolitinib, and now we have belumosudil [Rezurock] and axatilimab. For pediatric patients, there's the mesoblast product too [remestemcel-L; Ryoncil]. But I am interested in your algorithm, whether if you pick drugs based on symptoms or based on the line of therapy, and has anybody used a combination of these newer drugs?

Diaz-Paez: We decide whether we go with ruxolitinib or belumosudil with regards to second-line or third-line treatment for our patients, and regarding what organs are affected, how fast they're progressing, when they come in, and what staging they are….

If I can't get a medication, that will also impact it. But for the most part, there are a lot of patient assistance programs that tend to be fairly good about getting these medications for our patients. There have been some instances where we have started a patient on prednisone, and we figured we would start with belumosudil, and we might see progression in the GI tract or in some other organ that wasn't the primary initial manifestation. Then we've added ruxolitinib to the mix. Now they're on prednisone, belumosudil, and ruxolitinib in hopes of getting control, and then we start peeling off again hoping to try to get them down to 1 agent as the ultimate goal. We don't do that often. I would say there are fewer than 10 patients where I have them on both belumosudil and ruxolitinib; not a lot, but there is a small number.

Sdrimas: I also don't stop treatment to start belumosudil. I tend to start it while they're still on ruxolitinib and slowly taper the ruxolitinib if I don't see it working. In that scenario, I end up with using both of them at the same time for a while, and I haven't seen significant toxicities or significant increase in the infection risk throughout that process.

Diaz-Paez: I had a patient who presented with myositis, and then slowly progressed. She’s had ocular, vaginal, and some sclerotic features. We went through prednisone. We tried belumosudil and she had some adverse events with the belumosudil. We tried ruxolitinib and it didn’t work, and now I just have her on methotrexate once a week and she has been doing phenomenally. It's quite fascinating how the patients respond differently to all these agents. These agents have great results, and then for some patients, they don't work. Then you end up with other agents that we typically would not use commonly nowadays.

DISCLOSURES: There were no known relevant disclosures.

REFERENCES:

1. Zeiser R, Russo D, Ram R, et al. Ruxolitinib in patients with chronic graft-versus-host disease: three-year final analysis of efficacy and safety from the phase III REACH3 study. Blood. 2023;142(suppl 1):654. doi:10.1182/blood-2023-172590

2. Choe H, Salhotra A, Farhadfar N, et al. Dynamics of overall and organ-specific responses to axatilimab in chronic graft-versus-host disease: analysis from the Agave-201 study. Blood. 2024;144(suppl 1):98. doi:10.1182/blood-2024-209965