Ruxolitinib Demonstrates Early Efficacy in Chronic GVHD


Rushang D. Patel, MD, PhD, discusses the potential role of ruxolitinib in the treatment of patients with cGVHD. 

Rushang D. Patel, MD, PhD

Ruxolitinib (Jakafi) received FDA approval in May 2019 for the treatment of patients with steroid-refractory acute graft-versus-host-disease (aGVHD), but its utility in chronic GVHD (cGVHD) remains uncertain, said Rushang D. Patel, MD, PhD. However, findings from a single-center, retrospective study suggest that the first-in-class JAK1/2 inhibitor could be a safe and effective treatment for patients with cGVHD, even in those who are heavily pretreated.

"If patients with cGVHD are running out of options, ruxolitinib is a good option to use under careful monitoring," said Patel. "If patients are being cared for directly under the supervision of the transplant program, ruxolitinib can be used sooner rather than later."

Using a unique scoring system, the retrospective study presented at the 2020 Transplantation and Cellular Therapy Meetings revealed that 37% of events, defined as each organ involved in a patient, improved in severity after ruxolitinib. Additionally, 49% of events were deemed stable, 4% had worsened, and 10% were newly onset.

The majority of the 30 patients included in the study had undergone transplant for myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML), explained Patel.

Regarding safety, 8 patients required dose reductions, 6 of which were due to cytopenias. Two additional dose reductions were made for drug-interaction and rectal bleeding.

In an interview with OncLive, Patel, a bone marrow transplant and hematologic oncologist at Advent Health Cancer Institute, discussed the potential role of ruxolitinib in the treatment of patients with cGVHD.

OncLive: Please discuss aGVHD versus cGVHD.

Patel: GVHD in general is a major complication of stem cell transplants that can occur when a patient receives the stem cells from a donor despite improved techniques for finding an appropriate match.

GVHD is one of the major [complications that can result from] stem cell transplant. Symptoms of GVHD can be broadly divided into 2 categories. In aGVHD, the symptoms primarily involve the skin, gut, and liver. That usually happens within the first 100 days of the transplant. It can also happen later, but most cases occur within 100 days.

cGVHD can affect a number of organ systems, including the eyes, mouth, esophagus, skin, genitourinary organs, liver, and lungs. It can have a significant impact on a patient's quality of life (QOL). Although symptoms [of cGVHD] don’t progress as rapidly as in aGVHD, they have a major impact on the patient’s QOL.

Are steroids effective in treating patients with GVHD? Could ruxolitinib be used in this setting?

The only established frontline treatment for patients with aGVHD or cGVHD is steroids, which have their own set of complications. Many patients are steroid refractory or steroid dependent. There are patients who will respond to steroids but once we begin tapering the steroids, their symptoms return. It is often difficult to keep these patients on a high dose of steroids for an extended period of time because of the risk of infections, muscle weakening, and bone [loss].

A number of options are currently being used by clinicians for second and subsequent lines of treatment. The response rates to second-line treatments are not as good as we would like them to be; there is always room for better options in this space.

There has been some encouraging data with ruxolitinib in aGVHD. The big clinical trials that are using ruxolitinib for cGVHD have yet to fully mature, so we are awaiting data. [In the interim], we decided to use ruxolitinib for our patients with cGVHD who had progressed on multiple lines of treatment.

What patients were included in this study?

These were all adult patients. The majority had myeloid malignancies, specifically AML and MDS. We also included patients who had acute lymphoblastic leukemia and other reasons for which they underwent stem cell transplant. The majority of patients [underwent a] peripheral blood stem cell [transplant] and not bone marrow–derived stem cell [transplant]. The donors were a mixed bag of match-related, match-unrelated, and haploid-identical transplant patients.

We were pleasantly surprised to see the findings, because this was a heavily pretreated patient population. We presented some data on what patients’ prior treatments were. For example, 87% of our patients had already been exposed to high-dose steroids and required additional treatment.

What did the results show?

In this study, we saw some meaningful responses despite this being a challenging population to treat. Grading cGVHD and assessing the response [to treatment] is evolving. The National Institutes of Health (NIH) have taken the lead on that. They had 2 important meetings in 2005 and 2014, where they updated these criteria. The changes made [the criteria] more meaningful in assessing a patient's response to various new agents in clinical trials.

We have been using the NIH grading for organ systems, but once an individual organ is graded, how do we compile that data across 8 or 9 systems? What if there is improvement in 1 system, but instability in others? How do we grade them? That is another layer of analysis according to the NIH system, which is the global severity, scoring, and response assessment.

We did not use the NIH response assessment in the global severity calculations, and there are a couple of reasons for that. Those systems are designed for clinical trials where there is more support in terms of collecting data. In day-to-day practice, it is often difficult to use that global severity scoring system in the response criteria.

We used a simple, easily applied model where we calculated each organ that was involved in each patient as an event. Let's say a patient had involvement of the eyes, skin, and lungs. That would be counted as 3 events. Then, for each event, we assessed the cGVHD score before and after starting ruxolitinib. Wherever the score improved, we noted it as an improvement. Wherever the score remained stable, we noted it as stable. Whenever the disease worsened, we noted it as worsened. We also kept an account of which organ systems were not involved before starting ruxolitinib that became involved after starting ruxolitinib.

Using this simple system, we had 4 categories: improvement, stability, progression or worsening, and new onset. We found that about 36% of the events showed improvement [with ruxolitinib], 49% showed stability, and only 6% showed worsening. Interestingly, we found that about 10% of events were newly onset, meaning that 10 organs across these 30 patients that were not previously reported to be involved with GVHD became involved while the patient was on ruxolitinib.

What safety signals were found with ruxolitinib in this patient population?

Safety is always important in these patients because patients with cGVHD often end up on treatment for prolonged periods of time. Even if a treatment is very effective, it does not serve its purpose if it cannot be tolerated for a long time.

We found the ruxolitinib was very well tolerated. The major adverse effects (AEs) were related to decreased hemoglobin and platelet count. Additionally, there were a couple of cases where the patient's neutrophils decreased; [these were categorized as] cytopenias.

With dose interruptions and dose modifications, we were able to recover the patients from those toxicities. Only 1 patient required discontinuation of treatment due to rectal bleeding.

What is your advice to community oncologists who are treating patients with cGVHD?

cGVHD is a challenging situation to treat. It is often frustrating for the patient, and sometimes frustrating for the providers because we are not able to make the impact we would like.

Treatments are usually required for a long period of time. It's very important to monitor these patients closely for AEs, as well as worsening of symptoms, so that we can resolve them. Ruxolitinib is a good option to treat patients with cGVHD, according to what we have observed in our data. However, I recommend that we wait for final phase 3 data to confirm these findings. There was also a recent publication from Spain, which looked at the ruxolitinib experience across 13 centers. The numbers were quite similar to what we saw. As encouraging as these results are, it's always better to wait for the multicenter study to confirm the validity of the results.


  1. Patel RD, Browning A, Mori S, et al. Ruxolitinib is a safe and effective therapeutic option for management of chronic GVHD - a single center experience. Biol Blood Marrow Trans. 2020;26(suppl 3; abstr 285):S193-S194. doi:10.1016/j.bbmt.2019.12.761
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