TY - JOUR
T1 - Long-term treatment with ruxolitinib for patients with myelofibrosis
T2 - 5-year update from the randomized, double-blind, placebo-controlled, phase 3 COMFORT-I trial
AU - Verstovsek, Srdan
AU - Mesa, Ruben A
AU - Gotlib, Jason R
AU - Gupta, Vikas
AU - DiPersio, John F
AU - Catalano, John V.
AU - Deininger, Michael Werner Nikolaus
AU - Miller, Carole B
AU - Silver, Richard T
AU - Talpaz, Moshe
AU - Winton, Elliott F
AU - Harvey, Jimmie H
AU - Arcasoy, Murat O
AU - Hexner, Elizabeth Olson
AU - Lyons, Roger M
AU - Paquette, Ronald L
AU - Raza, Azra
AU - Jones, Mark
AU - Kornacki, Deanna
AU - Sun, Kang
AU - Kantarjian, Hagop M
PY - 2017/2/22
Y1 - 2017/2/22
N2 - Background: The randomized, double-blind, placebo-controlled, phase 3 COMFORT-I trial evaluated the JAK1/JAK2 inhibitor ruxolitinib in patients with intermediate-2/high-risk myelofibrosis. The primary and planned 3-year analyses of COMFORT-I data demonstrated that ruxolitinib - the first myelofibrosis-approved therapy - reduced splenomegaly and prolonged overall survival versus placebo. Here, we present the final 5-year results. Methods: Patients managed in Australia, Canada, and the USA were randomized centrally (interactive voice response system) 1:1 to oral ruxolitinib twice daily (15 or 20 mg per baseline platelet counts) or placebo. Investigators and patients were blinded to treatment. The secondary endpoints evaluated in this analysis were durability of a ≥35% reduction from baseline in spleen volume (spleen response) and overall survival, evaluated in the intent-to-treat population. Safety was evaluated in patients who received study treatment. Results: Patients were randomized (September 2009-April 2010) to ruxolitinib (n = 155) or placebo (n = 154). At termination, 27.7% of ruxolitinib-randomized patients and 25.2% (28/111) who crossed over from placebo were on treatment; no patients remained on placebo. Patients randomized to ruxolitinib had a median spleen response duration of 168.3 weeks and prolonged median overall survival versus placebo (ruxolitinib group, not reached; placebo group, 200 weeks; HR, 0.69; 95% CI, 0.50-0.96; P = 0.025) despite the crossover to ruxolitinib. The ruxolitinib safety profile remained consistent with previous analyses. The most common new-onset all-grade nonhematologic adverse events starting <12 versus ≥48 months after ruxolitinib initiation were fatigue (29.0 vs 33.3%) and diarrhea (27.8 vs 14.6%). New-onset grade 3 or 4 anemia and thrombocytopenia both primarily occurred within the first 6 months, with no cases after 42 months. The most common treatment-emergent adverse event-related deaths in the ruxolitinib-randomized group were sepsis (2.6%), disease progression (1.9%), and pneumonia (1.9%). Conclusion: The final COMFORT-I results continue to support ruxolitinib as an effective treatment for patients with intermediate-2/high-risk MF. Trial registration: ClinicalTrials.gov, NCT00952289
AB - Background: The randomized, double-blind, placebo-controlled, phase 3 COMFORT-I trial evaluated the JAK1/JAK2 inhibitor ruxolitinib in patients with intermediate-2/high-risk myelofibrosis. The primary and planned 3-year analyses of COMFORT-I data demonstrated that ruxolitinib - the first myelofibrosis-approved therapy - reduced splenomegaly and prolonged overall survival versus placebo. Here, we present the final 5-year results. Methods: Patients managed in Australia, Canada, and the USA were randomized centrally (interactive voice response system) 1:1 to oral ruxolitinib twice daily (15 or 20 mg per baseline platelet counts) or placebo. Investigators and patients were blinded to treatment. The secondary endpoints evaluated in this analysis were durability of a ≥35% reduction from baseline in spleen volume (spleen response) and overall survival, evaluated in the intent-to-treat population. Safety was evaluated in patients who received study treatment. Results: Patients were randomized (September 2009-April 2010) to ruxolitinib (n = 155) or placebo (n = 154). At termination, 27.7% of ruxolitinib-randomized patients and 25.2% (28/111) who crossed over from placebo were on treatment; no patients remained on placebo. Patients randomized to ruxolitinib had a median spleen response duration of 168.3 weeks and prolonged median overall survival versus placebo (ruxolitinib group, not reached; placebo group, 200 weeks; HR, 0.69; 95% CI, 0.50-0.96; P = 0.025) despite the crossover to ruxolitinib. The ruxolitinib safety profile remained consistent with previous analyses. The most common new-onset all-grade nonhematologic adverse events starting <12 versus ≥48 months after ruxolitinib initiation were fatigue (29.0 vs 33.3%) and diarrhea (27.8 vs 14.6%). New-onset grade 3 or 4 anemia and thrombocytopenia both primarily occurred within the first 6 months, with no cases after 42 months. The most common treatment-emergent adverse event-related deaths in the ruxolitinib-randomized group were sepsis (2.6%), disease progression (1.9%), and pneumonia (1.9%). Conclusion: The final COMFORT-I results continue to support ruxolitinib as an effective treatment for patients with intermediate-2/high-risk MF. Trial registration: ClinicalTrials.gov, NCT00952289
KW - JAK
KW - Janus kinase
KW - Myelofibrosis
UR - http://www.scopus.com/inward/record.url?scp=85013472843&partnerID=8YFLogxK
U2 - 10.1186/s13045-017-0417-z
DO - 10.1186/s13045-017-0417-z
M3 - Article
AN - SCOPUS:85013472843
SN - 1756-8722
VL - 10
SP - 1
EP - 14
JO - Journal of Hematology & Oncology
JF - Journal of Hematology & Oncology
IS - 1
ER -