Treating chronic graft-versus-host disease with ruxolitinib in both adult and pediatric patients was found to be safe and effective based on data from 2 separate single-center retrospective analyses whose results were presented during a poster session at the 2020 Transplantation & Cellular Therapy Meetings in Orlando, Florida.
Rushang D. Patel, MD
Treating chronic graft-versus-host disease (cGVHD) with ruxolitinib (Jakafi) in both adult and pediatric patients was found to be safe and effective based on data from 2 separate single-center retrospective analyses whose results were presented during a poster session at the 2020 Transplantation & Cellular Therapy Meetings in Orlando, Florida.1,2
“This is a challenging patient cohort to treat,” Rushang D. Patel, MD, of Advent Health in Orlando, Florida, said during the session. “These patients are emotionally distressed by the fact that they are in remission from leukemia, but they don’t have the quality of life that they were expecting after going through transplantation.”
Whereas acute GVHD and underlying hematologic malignancies threaten overall survival, the concern with cGVHD is centered around the significant impacts on a patient’s daily life. Patel said this can be especially troublesome in certain cases, such as for those who can no longer work long periods in front of a computer because of cGVHD affecting the eyes.
“The only [established] first-line approach is treatment with steroids,” Patel said. In refractory cGVHD, “ruxolitinib provides a good alternative compared to some other forms of therapy, such as photophoresis, because you don’t need to [administer] infusions, it does not cause that many infections, and the amount of monitoring required is not that high.”
Based on an analysis of 143 events in 30 patients with refractory cGVHD treated with ruxolitinib at the Blood and Marrow Transplant Center of Advent Health, there were 53 instances of improvement (37%) with ruxolitinib. Forty-nine percent (n = 70) of events were considered to be stable with only 6 events (4%) worsening with ruxolitinib. Fourteen (10%) new-onset events occurred during therapy.
Patel said that looking at the rates of improved and stable GVHD together, the responses are impressive. “These patients had been progressing on other treatments,” he said. “Had their symptoms for those particular organ systems [that had stabilized or improved with ruxolitinib] gotten worse, it would have been impactful on their quality of life.”
Each involved organ was considered an “event,” with each evaluable patient having ≥2 sites for analysis. Sixteen patients did not experience either worsening of or new-onset cGVHD, with 1 patient having a total of 5 sites of improvement.
Most patients with worsening or new-onset cGVHD in 1 or more organs also had improvement of GVHD in other areas. Two patients who experienced GVHD in the lungs were able to discontinue continuous oxygen use, which was notable given that GVHD to the lungs is considered irreversible.
“There are certain situations where, depending on what organ had worsening or new onset of GVHD, there might be available localized treatments,” Patel said, regarding the utility of ruxolitinib for patients who experience worsening of cGVHD in 1 area, but improvements elsewhere. “If new onset of worsening GVHD was in an organ such as the lung, then you are not going to keep that patient on treatment. However, if there are topical treatments available [to treat worsening symptoms], you can add it to their treatment if ruxolitinib is leading to a response in other areas.”
Of note, Patel said rates of adverse events were low. “We didn’t observe significant toxicity,” he said. “You mainly have to watch for [cytopenias] and drug interactions.”
Dose reductions were required in a total of 8 patients. Reasons for dose reductions were cytopenias in 6 patients, and 1 each for drug interactions and rectal bleeding. Only 1 patient discontinued treatment permanently.
Twenty-three patients treated in the study were those with acute myeloid leukemia (n = 14) or myelodysplastic syndrome (n = 9); 3 patients had acute lymphoblastic leukemia; and 1 each had chronic myeloid leukemia, chronic myelomonocytic leukemia, Hodgkin lymphoma, and myelofibrosis. Patients either received matched related donor (n = 14) or matched unrelated donor (n = 13), haploidentical (n = 2), or mismatched unrelated donor transplant (n = 1). The source was peripheral blood stem cells in 28 and bone marrow in 1.
Prior GVHD regimens in this group included steroids (87%), sirolimus (63%), tacrolimus (40%), extracorporeal photophoresis (40%), rituximab (Rituxan; 37%), ibrutinib (Imbruvica; 20%), imatinib (20%), mycophenolate mofetil (Myfortic; 7%), cyclosporine (7%), and interleukin-2 (3%).
In a separate retrospective analysis of 15 pediatric and young adult patients treated at Stanford Children’s Health, responses to ruxolitinib as salvage and steroid-sparing treatment were observed in both patients with steroid-refractory acute GVHD and cGVHD.
In the 10 patients with cGVHD, the overall response rate (ORR) was 78%. Of the 9 patients with cGVHD who were evaluable for response, 7 responding patients had a median treatment duration of 264 days (range, 164-490).
Four out of 9 evaluable patients developed ≥1 infection during the treatment period, including cytomegalovirus reactivation, respiratory syncytial virus, influenza, rhino/enterovirus, nonspecific upper respiratory tract infection, norovirus, and bacterial infection. Dose-limiting toxicities in this group were cytopenias (22%). One patient had a severe allergic reaction.
Patients in this cohort had experience with a median of 3 prior agents (range, 2-6) before ruxolitinib use.
With close monitoring of infections and myelosuppression, real-world evidence from these 2 patients cohorts suggest ruxolitinib may be a viable option for treating cGVHD.