Early Initiation of Ruxolitinib Reduces Risk, Severity of aGVHD

Initiating ruxolitinib treatment early on can lower the risk and severity of acute graft-versus-host disease (aGVHD) in patients with acute leukemia undergoing alternative donor hematopoietic stem cell transplantation (HSCT), found a new study published in Scientific Reports.

The study of 57 patients with aGVHD also showed they tolerated the treatment, offering promise for preventing and managing the complication of transplantation, which affects up to half of patients.

“Alternative donors remain an important source. Alternative donor–HSCT has achieved good results; the 4-year overall survival (OS) and disease-free survival (DFS) can be more than 80%,” explained the researchers. “However, transplant-related complications are still pivotal factors decreasing the success of transplantation. Especially aGVHD is still a common serious complication of allo-HSCT, seriously affecting the survival and prognosis of patients.”

The group of patients included in the study were split up to receive either ruxolitinib (n = 41) or to receive aGVHD prohphylaxis with cyclophosphamide, antithymocyte globulin-Fresenius, cyclosporine A, and mycophenolate mofetil (controls; n = 16).

Patients receiving ruxolitinib were approximately half as likely to experience a GVHD (22% vs 50%). They were also significantly less likely to experience grade 3-4 disease (7.3% vs 28.6%).

Between the 2 groups, there were no significant differences in incidence of chronic GVHD; hemorrhagic cystitis; pulmonary, intestinal, Epstein-Barr virus, or cytomegalovirus infection; relapse; death; or nonrelapse mortality.

“Although ruxolitinib had a significant effect on the prevention and treatment of GVHD, some problems still needed to be resolved,” noted the researchers. “First, the perfect time to apply ruxolitinib to prevent GVHD: Are neutrophils implanted, or both neutrophils and platelets implanted? Second, the perfect time to discontinue ruxolitinib: Can we quickly discontinue other immunosuppressants instead of stopping ruxolitinib to reduce the incidence of infection without significant cytopenia after engraftment?”

Fifty-five of the patients achieved reconstitution of hematopoiesis; 2 patients in the control group experienced failure as a result of early graft rejection and serious infection. There were no significant differences in survival, with a 2-year OS rate of 42.9% among controls and a 53.7% 2-year OS rate among those receiving ruxolitinib. Two-year DFS was 32.1% among controls and 46.3% among patients receiving ruxolitinib.

Large multicenter randomized clinical trials should be conducted to validate their findings, the authors concluded.

Reference

Zhang B, Chen L, Zhou J, et al. Ruxolitinib early administration reduces acute GVHD after alternative donor hematopoietic stem cell transplantation in acute leukemia. Sci Rep. 2021;11(1):8501. doi:10.1038/s41598-021-88080-3