Ruxolitinib Shows Efficacy in Patients With Steroid-Resistant, Dependent Chronic GVHD

The new data provide hope that the therapy will prove effective for a patient group with limited options.

Ruxolitinib (Jakafi) is effective for moderate or severe steroid-refractory or steroid-dependent chronic graft-versus-host disease (cGVHD), according to newly released phase 3 study data.

The findings, released during the American Society of Hematology’s 62nd Annual Meeting and Exposition, suggest a new therapy may soon be available for patients in an underserved patient group.1

Patients who suffer cGVHD are typically treated with therapy that includes systemic corticosteroids. However, roughly half of those patients will become steroid refractory or steroid dependent, and there is no clear second-line option available for these patients, according to presenting author Robert Zeiser, MD, of the University of Freiburg.

“The damaging and sometimes deadly effects of chronic GVHD following stem cell transplantation present significant treatment challenges, particularly for patients who do not respond to steroid treatment,” Zeiser said.

Ruxolitinib is a Janus kinase 1/2 inhibitor. In a previous phase 3 study (REACH2), it was superior to the best available therapy (BAT) in patients with steroid-refractory acute GVHD.2

In the new study (REACH3), the authors sought to find out whether the drug could also beat BAT in patients with the chronic form of the disease.

The study was an open-label, randomized study in which ruxolitinib was compared to BAT. A total of 329 patients were included in the study, with 165 given 10 mg ruxolitinib twice daily and 164 treated with one of 10 BAT options. Patients were treated for 6 28-day cycles. The patients were all at least 12 years of age, had received allogeneic hematopoietic cell transplant, and had developed moderate or severe steroid-refractory or steroid-dependent cGVHD.

Patients who had previously been given JAK inhibitors for acute GVHD were permitted into the study if they had achieved partial or complete responses and had not taken the JAK inhibitor within the 8 weeks prior to the start of the first cycle of therapy for the new study. Patients with 2 or more lines of prior systemic therapy for cGVHD in addition to corticosteroids with or without calcineurin inhibitors were excluded from the study.

The primary endpoint was overall response rate (ORR). At week 24, ruxolitinib had a 49.7% ORR, roughly double the 25.6% ORR of BAT.

“These data are important for patients living with GVHD and their physicians as they represent the continued success of Jakafi in the chronic form of the disease, a historically difficult-to-treat condition,” said Peter Langmuir, MD, group vice president for Oncology Targeted Therapies at Incyte, the drug’s developer.

Among the study’s secondary endpoints, ruxolitinib had superior failure-free survival (median not reached versus 5.7 months in BAT). In the study failure-free survival was defined as time to earliest recurrence of the underlying disease. the start of new systemic treatment for chronic GVHD, or death.

Patients in the ruxolitinib group also had greater reductions in patient-reported symptoms and a median duration of response that was not yet reached, versus 6.2 months in the BAT arm.

The study found no new safety signals for the drug. The most common adverse events with ruxolitinib were anemia (29.1% in ruxolitinib versus 12.7% for BAT), hypertension (15.8% versus 12.7%) and pyrexia (15.8% versus 9.5%). Just over one-third of patients (37.6%) in the ruxolitinib arm and 16.5% of patients in the BAT arm required dose modifications; the rate of discontinuation due to AEs was 16.4% and 7%, respectively.


  1. Zeiser R, Bubnoff NV, Butler J, et al. Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease. N Engl J Med. 2020;382(19):1800-1810. doi:10.1056/nejmoa1917635
  2. Zeiser R. Ruxolitinib (RUX) Vs best available therapy (BAT) in patients with steroid-refractory/steroid-dependent chronic graft-vs-host disease (cGVHD): Primary findings from the phase 3, randomized REACH3 study. Published December 5, 2020. Accessed December 5, 2020.