TY - JOUR
T1 - Long-term outcomes of 107 patients with myelofibrosis receiving JAK1/JAK2 inhibitor ruxolitinib
T2 - Survival advantage in comparison to matched historical controls
AU - Verstovsek, Srdan
AU - Kantarjian, Hagop M.
AU - Estrov, Zeev
AU - Cortes, Jorge E.
AU - Thomas, Deborah A.
AU - Kadia, Tapan
AU - Pierce, Sherry
AU - Jabbour, Elias
AU - Borthakur, Gautham
AU - Rumi, Elisa
AU - Pungolino, Ester
AU - Morra, Enrica
AU - Caramazza, Domenica
AU - Cazzola, Mario
AU - Passamonti, Francesco
PY - 2012/8/9
Y1 - 2012/8/9
N2 - 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 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 = .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.
AB - 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 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 = .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.
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U2 - 10.1182/blood-2012-02-414631
DO - 10.1182/blood-2012-02-414631
M3 - Article
C2 - 22718840
AN - SCOPUS:84865192181
SN - 0006-4971
VL - 120
SP - 1202
EP - 1209
JO - Blood
JF - Blood
IS - 6
ER -