WHAT WAS LEARNED
At day 56, durable ORRs were higher in the ruxolitinib group (40%) compared with the control group (22%; odds ratio, 2.38; 95% CI, 1.43 to 3.94; P <.001). At 6 months, the estimated cumulative incidence of loss of response was found to be 10% in the ruxolitinib group and 39% in the control group. “Ruxolitinib was more efficient at inducing a response at day 28 and day 56 compared with BAT. This is the first phase 3 study showing that a treatment for steroid-refractory GVHD is improving efficacy so it was a positive surprise to the community,” said study investigator Robert Zeiser, MD, of the University Hospital Freiburg, Department of Haematology, Oncology and Stem Cell Transplantation, Freiburg, Germany.
Median failure-free survival was 5.0 months with ruxolitinib and 1.0 months for the control group, and median OS was 11.1 months in the ruxolitinib group and 6.5 months in the control group (hazard ratio for death, 0.83; 95% CI, 0.60 to 1.15). The current investigation turned up no new safety signals, and the ruxolitinib safety profile in REACH2 was consistent with what has been reported previously.
In the ruxolitinib group, 38% of patients required dose modifications, whereas dose modifications were required in 9% in the control group. However, the number of patients who discontinued treatment due to adverse events was low (11% in the ruxolitinib group and 5% in the control group, respectively). The most common adverse events up to day 28 included thrombocytopenia (33% and 18%), anemia (30% and 28%), and cytomegalovirus infection (26% and 21%).
IMPLICATIONS FOR NURSES
Acute GVHD is a serious and common condition associated with high mortality. These patients face life-threatening challenges with limited treatment options, Dr Zeiser explained. However, these new data showing superiority of ruxolitinib over current standard-of-care therapies add to a growing body of evidence that targeting the JAK pathway may be an effective strategy in this difficult-to-treat population. Most deaths were attributed to aGVHD (22% in the ruxolitinib group and 25% in the control group). The most commonly reported causes of death were underlying disease progression, including neoplasms (8 patients in the ruxolitinib group and 8 in the control group), multiple organ dysfunction syndrome (3 in ruxolitinib group and 1 in control group), sepsis (4 in ruxolitinib group and 3 in control group), and septic shock (3 in each group).
“This study was large enough to be practice changing. Also, the side effects were manageable and expected,” Dr Zeiser reported (email communication, May 2020). “I have talked to nurses on our wards, and they stated that before ruxolitinib we hardly saw any grade 4 steroid refractory GVHD patients surviving. Since ruxolitinib is part of the treatment at least a fraction of these patients survive.”
Dr Zeiser believes that oncology nurses’ awareness that ruxolitinib is part of the therapeutic armamentarium against GVHD when a patient does not respond to glucocorticoids is paramount. He emphasized that close monitoring of platelets and cytomegalovirus reactivation in this patient population is very important.
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. doi:10.1056/NEJMoa1917635