The Chronic GVHD Treatment Paradigm

EP: 1.Graft versus Host Disease Background

EP: 2.Overview of GVHD Risk Factors

EP: 3.Current GVHD Prophylaxis Strategies

EP: 4.Signs and Symptoms of Acute and Chronic GVHD

EP: 5.Statistics on the Incidence of Chronic GVHD

EP: 6.Identification of Patients at High Risk for GVHD

EP: 7.Assessment of Chronic GVHD Symptoms

EP: 8.The NIH Clinical Scoring of Organ Systems

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EP: 9.The Chronic GVHD Treatment Paradigm

EP: 10.Patient Case: A 48-Year-Old Man with Chronic GVHD

EP: 11.Treatment Goals for a Patient With Chronic GVHD

EP: 12.Steroid-Refractory Chronic GVHD Background

EP: 13.Therapy Options for Steroid-Refractory Chronic GVHD

EP: 14.Ibrutinib as Second-Line Therapy for Steroid-Refractory Chronic GVHD

EP: 15.The iNTEGRATE Trial: Ibrutinib With Prednisone as First-Line Therapy for cGVHD

EP: 16.The REACH3 Clinical Trial of Ruxolitinib in Chronic GVHD

EP: 17.Clinical Experience with Ruxolitinib for cGVHD

EP: 18.The ROCKstar Study of Belumosudil in cGVHD

EP: 19.Real-World Experience with Belumosudil

EP: 20.Summary of Axatilimab for cGVHD

EP: 21.Therapy Selection for Patients with Chronic GVHD

EP: 22.Discussion of Long-Term Effects of GVHD Therapy

EP: 23.Future Directions in Graft Versus Host Disease

Transcript:

Yi-Bin Chen, MD: But if we talk about sort of treatment for chronic graft-versus-host disease [GVHD], Catherine, I wanted to ask you to take us through how you view treatment, depending on the degree of chronic graft-versus-host disease and how you start.

Catherine J. Lee, MD, MS: I’m happy to. So for patients who we diagnose with mild former chronic GVHD—this would be the overall global score mild—what we usually do is just use topical creams or ointments or ophthalmic drops. For example, if a patient presented with skin manifestations of chronic GVHD, such as a localized rash, fulfilling score 1 or mild chronic GVHD, the overall global severity, we may prescribe triamcinolone cream or ointment, or maybe a higher potency steroid, topical steroid cream, such as clobetasol. For patients who present with dry eyes, we would initially start with recommending artificial tears and possibly use of steroid eyedrops or something such as Restasis [cyclosporine] eye drops. Patients who then progress or who present with moderate-to-severe symptoms, warrant systemic treatment with immunosuppression and the current standard of care for first line or upfront treatment is still corticosteroids.

Usually at a dose starting between 0.5 mg per kg per day up to 1 mg per kg per day. Interestingly, I’ve had some colleagues tell me that they will sometimes use up to 2 mg per kg per day. But I would say, overall, I think most providers would probably maximize a dose at 1 mg per kg per day. And so, when using steroids typically, you know, these patients are in the outpatient setting and we try to make it convenient for them. So we usually prescribe oral prednisone, and would, at least in my practice, I give this a trial for about 1-2 weeks. If I find that patients’ signs and symptoms are progressing towards the 2-week mark, I essentially feel that they are refractory to corticosteroids and then I may initiate second-line treatment at that time. As well, there are other criteria for patients who may have an initial response, but then whose disease stabilizes out, you know, over a month…and I believe we’re going to be getting to this on the next few slides, but patients who are steroid dependent, that might also qualify for second-line treatment. During this time, when patients are on high-dose steroids, it’s very important to keep in mind infection prophylaxis as patients are at risk for developing bacterial, viral, or fungal infections.

Our patients are definitely on prophylaxis for HSV [herpes simplex virus] or VZV [varicella-zoster virus] infection. So, either with valacyclovir or Valtrex. For patients at some institutions, especially if they have a history of CMV [cytomegalovirus] viremia or infection, some institutions may reuse letermovir [Prevymis] for CMV prophylaxis while patients are on high-dose steroids. I have done that while I was at the Huntsman Cancer [Institute], and some of this is also dependent on whether insurance will approve the use of letermovir in this setting. As well, you want to be vigilant for any fungal infections and prevent this from happening. So for patients who are or plan to be on high-dose steroids for a while, it's important to use antifungals that will cover for mold organisms. Typically, we would use posaconazole or voriconazole, and then when this prednisone dose drops below 0.5 mg per kg per day, or at some centers, less than 10 mg per day, some centers may then transition the antifungal to fluconazole to cover for just candida.

Lastly, patients should be covered for PJP [Pneumocystis jiroveci pneumonia] and should be optimally placed on Bactrim [trimethoprim/sulfamethoxazole] if it’s well tolerated. Otherwise, other options include dapsone or IV or inhaled pentamidine. And then, also very important in the treatment is providing other supportive care, so things like physical therapy or massage, occupational therapy are really crucial in keeping the patient’s function intact, particularly for patients who have sclerotic forms of chronic GVHD. Having a physical therapist evaluate them for individualized stretching exercises as well as other functional movement can be very useful for the patient.

Yi-Bin Chen, MD: I mean you’ve definitely illustrated that we unfortunately still [are] stuck with steroids as first-line care and there are necessary evils that come with that, and that’s why a huge push here is to figure out how do we get beyond it. You know, this slide, [there’s] sort of a lot of the options that we’ve used through the years and that we’ve recently started to use for steroid-refractory chronic graft-versus-host disease that we will discuss specifically. I think the thing to point out is that some of these agents, we are now going to be moving into the frontline setting as part of clinical trials to see if they can one day replace steroids for certain phenotypes or subsets of patients. I think that’s a huge, huge push for many of us to improve the care because steroids, while they do help some patients, they do create a lot of harm for our patients, especially those with chronic graft-versus-host disease.

Transcript edited for clarity.