Multicenter phase 3 trial of low-dose ruxolitinib for graft-versus-host disease prevention in haploidentical HSCT

Acute graft-versus-host disease (aGVHD) is a major cause of morbitidy and mortality after haploidentical hematopoietic stem-cell transplantation (HSCT). For standard prophylaxis of aGVHD, combination of antithymocyte globulin, a calcineurin inhibitor, short-course methotrexate, and mycophenolate mofetil. A phase 3 trial at five centers in China evaluated whether replacing of mycophenolate by low-dose ruxolitinib could reduce aGVHD after haploidentical HSCT. A total of 215 patients were randomly assigned, of whom 206 were included in the ITT population (103 in the ruxolitinib prophylaxis group and 103 in the standard prophylaxis group). Among surviving patients, the median follow-up was 26.4 months (IQR 20.0-33.3). By day 100, grade II-IV aGVHD occurred in seven patients in the ruxolitinib prophylaxis group and 38 patients in the standard prophylaxis group (sHR 0.15; p<0.0001). The most common grade 3-4 adverse events in the ruxolitinib prophylaxis group and the standard prophylaxis group werethrombocytopenis (17% versus 11%), neutropenia (14% versus 9%), anemia (12% versus 9%), and cystitis (7% versus 10%), with serious adverse events occurring in 30% versus 35%. No fatal adverse events occurred in the ruxolitinib prophylaxis group, whereas three deaths occurred in the standard prophylaxis group. The authors conclude that low-dose ruxolitinib, used in place of mycophenolate mofetil within a backbone of prophylactic antithymocyte globulin, calcineurin inhibitor, and short-course methotrexate, reduced grade II-IV aGVHD by day 100 after hapolidentical HSCT and had manageable toxicity.