CLINICAL TRIALS AND OBSERVATIONS Long-term outcomes of 107 patients with myelofibrosis receiving JAK1/JAK2 inhibitor ruxolitinib: survival advantage in comparison to matched historical controls

Ruxolitinib is JAK1/JAK2 inhibitor with established clinical benefit in myelofibrosis (MF). We analyzed long-term outcomes of 107 patients with intermediate-2 or high-risk MF receiving ruxolitinib at MD Anderson Cancer Center (MDACC) on phase 1/2 trial. After a median of 32 months of follow-up, 58 patients (54%) were still receiving ruxolitinib, with overall survival (OS) of 69%. The splenomegaly and symptom reductions achieved with ruxolitinib were sustained with longterm therapy. Therapy was well tolerated; discontinuation rates at 1, 2, and 3 years were 24%, 36%, and 46%, respectively. OS of 107 MDACC patients was significantly better (P .005) than that of 310 matched (based on trial enrollment criteria) historical control patients, primarily because of highly significant difference in OS in the high-risk subgroup (P .006). Furthermore, among MDACC patients, those with high-risk MF experienced the same OS as those with intermediate-2 risk. Patients with > 50% reduction in splenomegaly had significantly prolonged survival versus those with < 25% reduction (P < .0001). Comparison of discontinuation rates and reasons for stopping the therapy to those reported for other 51 patients in the phase 1/2 trial, and 155 ruxolitinib-treated patients in phase 3 COMFORT-I study, suggest that continued therapy with ruxolitinib at optimal doses contributes to the benefits seen, including OS benefit. (Blood. 2012;120(6):1202-1209)