Acknowledging Different Considerations for Ruxolitinib in Severe GVHD

News
Article

In the second article of a 2-part series, Lori Muffly, MD, MS, leads a discussion on how treatment considerations change when a patient has severe graft-vs-host disease or if the involvement is in the lung and where ruxolitinib fits into treatment.

Lori Muffly, MD, MS​

Hematologist, Blood and marrow transplant specialist

Hematologist-Oncologist

Associate Professor of Medicine

Blood and Marrow Transplantation and Cellular Therapy

Stanford University​

Lori Muffly, MD, MS​

Hematologist, Blood and marrow transplant specialist

Hematologist-Oncologist

Associate Professor of Medicine

Blood and Marrow Transplantation and Cellular Therapy

Stanford University​

CASE SUMMARY

A 48-year-old man underwent a myeloablative conditioning matched unrelated donor allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML) with tacrolimus plus methotrexate as graft-vs-host-disease (GVHD) prophylaxis​. The donor was a cytomegalovirus seropositive 33-year-old woman with 3 children. Over 22 days after transplantation, acute GVHD of the skin emerged and was successfully treated with a slow steroid taper​. Three months after transplantation, a bone marrow biopsy confirmed his AML was in remission, and between 3 to 6 months after transplantation, the patient was then successfully tapered off tacrolimus.

Seven months after transplantation, the patient returned with complaints of new onset cutaneous changes marked by hyperpigmentation, xerostomis, and mild ocular discomfort. Approximately one-half of each arm exhibited lichen-planus. Superficial sclerotic features (able to pinch the skin) were evident on the lower trunk and lower extremities. His body surface area involvement was 18%. Pulmonary function tests showed no decrease in forced expiratory volume in 1 second/carbon monoxide lung diffusion capacity and his blood counts and laboratory profiles were within normal limits.

DISCUSSION QUESTION

  • How would your approach to treatment change if the patient in this case met the criteria for severe chronic GVHD? Or if they had involvement elsewhere?

LORI MUFFLY, MD, MS​: Would you change your approach if the patient met criteria for severe chronic GVHD, or if the patient had lung involvement? Would you still use ruxolitinib [Jakafi] in that case? Or would there be [another] agent you add?

CATHERINE LEE, MD: We've heard...that belumosudil [Rezurock] may be better for [patients with bronchiolitis obliterans syndrome (BOS)], but when you look at recent data...no one responded to belumosudil if they had advanced BOS.1 Everyone who had early BOS...could respond to belumosudil, but these people probably also respond to ruxolitinib as well. There are more data coming out demystifying that belumosudil should be the go-to drug for [patients with] BOS. One has to keep in mind that the REACH2 trial [NCT02913261] was the only randomized trial out of the available agents, and so there were clear data showing that ruxolitinib was superior to all the best alternative therapies,2 whereas the ROCKstar [NCT03640481] trial had no comparison group.3

MUFFLY: Anyone else have thoughts on [treating patients with] severe or lung GVHD?

PRASHANT SHARMA, MD: I've never used belumosudil before ruxolitinib. Is that something you have done before? We've done it the other way around, but never belumosudil before ruxolitinib.

MUFFLY: I usually use ruxolitinib first, but there are a handful of cases where I don't and that's usually when a patient is presenting with more of a sclerotic-type GVHD. [This is] where the patient doesn’t have much inflammation and their eyes and mouth are fine, but they're tight still. I have started a few different patients on belumosudil, and...usually for my [patients with] primary lung GVHD...I use belumosudil rather than ruxolitinib. I have had almost no success with using ruxolitinib [for patients with] lung GVHD, so I think it's my own bias. But usually it's the other way around, and I will say we put out data...where we often use [belumosudil and ruxolitinib] together.4 I have several patients who are on both, and those are usually the patients that aren't responding the way we want them to.

LEE: I agree with that statement. Many [physicians] are using belumosudil before ruxolitinib if insurance will approve it…. In terms of combination therapy, we presented some data that showed combination therapy with ruxolitinib and belumosudil was safe and feasible.5 In my personal practice, I have seen some additional response [with this combination], although I have not seen clear reversibility of severe chronic GVHD.

JI-LIAN CAI, MD: If a patient has very severe gastrointestinal GVHD with [significant] diarrhea, will they still absorb the oral medication like belumosudil and ruxolitinib?

MUFFLY: The first area [ruxolitinib] was tested in for the GVHD spectrum was steroid-refractory acute GVHD,6 and that's mostly [seen in the] bowels. I don't know the absorption data, but it has an approval in that space, which suggests that there is absorption.7 I have no idea about belumosudil [absorption in that case]. I don't see a lot of patients with chronic GVHD that are unable to absorb [therapy] due to diarrhea, but I don't know if others see that. I have very few, if any, patients that are in that situation. I do have a couple of patients, though, that have feeding tubes because of esophageal stricture and that's a terrible thing.

LEE: I don't see massive diarrhea in the clinic where you can see pills coming out in the stool. But that is something to ask patients, whether they see pills coming out in the stool, or if they have an ostomy bag [then you should ask] whether they see any tablets or pills coming out in their bag. So, in those situations, you may consider not using those drugs.

References

1. DeFilipp Z, Kim HT, Yang Z, Noonan J, Blazar BR, Lee SJ, Pavletic SZ, Cutler C. Clinical response to belumosudil in bronchiolitis obliterans syndrome: a combined analysis from 2 prospective trials. Blood Adv. 2022;6(24):6263-6270. doi:10.1182/bloodadvances.2022008095

2. Zeiser R, von Bubnoff N, Butler J, et al; REACH2 Trial Group. Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease. N Engl J Med. 2020;382(19):1800-1810. doi:10.1056/NEJMoa1917635

3. Cutler C, Lee SJ, Arai S, et al. Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar Study. Blood. 2021;138(22):2278-2289. doi:10.1182/blood.2021012021

4. Chin M, Shizuru JA, Muffly L, et al. Belumosudil combination therapy in refractory chronic graft-versus-host disease. Blood. 2022;140(1):4788-4789. doi:10.1182/blood-2022-165547

5. Pusic I, Lee C, Veeraputhiran M, Minor C, DiPersio JF. Belumosudil and ruxolitinib combination for treatment of refractory chronic graft-versus-host disease. Bone Marrow Transplant. 2024;59(2):282-284. doi:10.1038/s41409-023-02165-3

6. Zhang MY, Zhao P, Zhang Y, Wang JS. Efficacy and safety of ruxolitinib for steroid-refractory graft-versus-host disease: Systematic review and meta-analysis of randomised and non-randomised studies. PLoS One. 2022;17(7):e0271979. doi:10.1371/journal.pone.0271979

7. FDA approves ruxolitinib for acute graft-versus-host disease. FDA. News release. May 24, 2019. Accessed February 23, 2024. http://tinyurl.com/vusbrpdw

Related Videos
Gary J. Schiller, MD, an expert on MDS
Gary J. Schiller, MD, an expert on MDS
Gary J. Schiller, MD, an expert on MDS
Gary J. Schiller, MD, an expert on MDS
Gary J. Schiller, MD, an expert on MDS
Gary J. Schiller, MD, an expert on MDS
A panel of 3 experts on GVHD
A panel of 3 experts on GVHD
Related Content