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 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 I/II trial. After a median 32 months 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 long-term 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=0.005) 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=0.006). 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 vs. those with <25% reduction (p<0.0001). Comparison of discontinuation rates and reasons for stopping the therapy to those reported for other 51 patients in the Phase I/II trial, and 155 ruxolitinib-treated patients in Phase III COMFORT-I study, suggest that continued therapy with ruxolitinib at optimal doses contributes to the benefits seen, including OS benefit.