TY - JOUR
T1 - Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts
AU - Talpaz, Moshe
AU - Paquette, Ronald
AU - Afrin, Lawrence
AU - Hamburg, Solomon I.
AU - Prchal, Josef T.
AU - Jamieson, Katarzyna
AU - Terebelo, Howard R.
AU - Ortega, Gregory L.
AU - Lyons, Roger M.
AU - Tiu, Ramon V.
AU - Winton, Elliott F.
AU - Natrajan, Kavita
AU - Odenike, Olatoyosi
AU - Claxton, David
AU - Peng, Wei
AU - O'Neill, Peter
AU - Erickson-Viitanen, Susan
AU - Leopold, Lance
AU - Sandor, Victor
AU - Levy, Richard S.
AU - Kantarjian, Hagop M.
AU - Verstovsek, Srdan
N1 - Funding Information:
M.T. received research funding from Incyte Corporation and consultancy fees from Sanofi as a member of an advisory board; R.P. received consulting fees paid through his institution from Incyte Corporation; L.A., S.I.H., J.T.P., K.N., and D.C. have no relationships to disclose; H.R.T. received honoraria from Celgene, Millenium, and Amgen for speaking and consultancy fees for advisory board membership from Celgene; K.J. received membership on an entity’s Board of Directors or advisory committees from Sunesis and consultancy fees from Blue Distinction Centers for Transplants and BlueCross BlueShield Association; G.L.O. received research funding from Incyte Corporation; R.M.L. received grant support through his institution from Incyte Corporation; R.V.T., serves on speakers bureau from Incyte Corporation; E.F.W. received support through his institution from Incyte Corporation and Sanofi-Aventis; O.O. received grant support through her institution from Incyte Corporation, grant support for clinical trials from S*Bio, NS Pharma, Celgene, and Novartis, membership on an entity’s advisory committees from Incyte Corporation, Sanofi-Aventis, Spectrum Pharmaceuticals, and Sunesis, and honoraria for CME-related speaking engagements and research support from Topotarget and Eisai; W.P., P.O., L.L., V.S., and R.S.L. are employees of Incyte Corporation and own stock in Incyte Corporation; S.E.-V. is a former employee of Incyte Corporation and owns stock in Incyte Corporation; H.M.K. received grant support through his institution from Incyte Corporation; S.V. received grant support through his institution from Incyte Corporation, Exelixis, Celgene, NS Pharma, Infinity Pharmaceuticals, SBIO, Lilly Oncology, AstraZeneca, Geron, Bristol-Myers Squibb, YM BioSciences, Gilead, and Roche.
PY - 2013
Y1 - 2013
N2 - Background: Ruxolitinib, a Janus kinase 1 and 2 inhibitor, demonstrated improvements in spleen volume, symptoms, and survival over placebo and best available therapy in intermediate-2 or high-risk myelofibrosis patients with baseline platelet counts ≥100 × 109/L in phase III studies. The most common adverse events were dose-dependent anemia and thrombocytopenia, which were anticipated because thrombopoietin and erythropoietin signal through JAK2. These events were manageable, rarely leading to treatment discontinuation. Because approximately one-quarter of MF patients have platelet counts <100 × 109/L consequent to their disease, ruxolitinib was evaluated in this subset of patients using lower initial doses. Interim results of a phase II study of ruxolitinib in myelofibrosis patients with baseline platelet counts of 50-100 × 109/L are reported. Methods. Ruxolitinib was initiated at a dose of 5 mg twice daily (BID), and doses could be increased by 5 mg once daily every 4 weeks to 10 mg BID if platelet counts remained adequate. Additional dosage increases required evidence of suboptimal efficacy. Assessments included measurement of spleen volume by MRI, MF symptoms by MF Symptom Assessment Form v2.0 Total Symptom Score [TSS]), Patient Global Impression of Change (PGIC); EORTC QLQ-C30, and safety/tolerability. Results: By week 24, 62% of patients achieved stable doses ≥10 mg BID. Median reductions in spleen volume and TSS were 24.2% and 43.8%, respectively. Thrombocytopenia necessitating dose reductions and dose interruptions occurred in 12 and 8 patients, respectively, and occurred mainly in patients with baseline platelet counts ≤75 × 109/L. Seven patients experienced platelet count increases ≥15 × 109/L. Mean hemoglobin levels remained stable over the treatment period. Two patients discontinued for adverse events: 1 for grade 4 retroperitoneal hemorrhage secondary to multiple and suspected pre-existing renal artery aneurysms and 1 for grade 4 thrombocytopenia. Conclusions: Results suggest that a low starting dose of ruxolitinib with escalation to 10 mg BID may be appropriate in myelofibrosis patients with low platelet counts. Trial registration. ClinicalTrials.gov: NCT01348490.
AB - Background: Ruxolitinib, a Janus kinase 1 and 2 inhibitor, demonstrated improvements in spleen volume, symptoms, and survival over placebo and best available therapy in intermediate-2 or high-risk myelofibrosis patients with baseline platelet counts ≥100 × 109/L in phase III studies. The most common adverse events were dose-dependent anemia and thrombocytopenia, which were anticipated because thrombopoietin and erythropoietin signal through JAK2. These events were manageable, rarely leading to treatment discontinuation. Because approximately one-quarter of MF patients have platelet counts <100 × 109/L consequent to their disease, ruxolitinib was evaluated in this subset of patients using lower initial doses. Interim results of a phase II study of ruxolitinib in myelofibrosis patients with baseline platelet counts of 50-100 × 109/L are reported. Methods. Ruxolitinib was initiated at a dose of 5 mg twice daily (BID), and doses could be increased by 5 mg once daily every 4 weeks to 10 mg BID if platelet counts remained adequate. Additional dosage increases required evidence of suboptimal efficacy. Assessments included measurement of spleen volume by MRI, MF symptoms by MF Symptom Assessment Form v2.0 Total Symptom Score [TSS]), Patient Global Impression of Change (PGIC); EORTC QLQ-C30, and safety/tolerability. Results: By week 24, 62% of patients achieved stable doses ≥10 mg BID. Median reductions in spleen volume and TSS were 24.2% and 43.8%, respectively. Thrombocytopenia necessitating dose reductions and dose interruptions occurred in 12 and 8 patients, respectively, and occurred mainly in patients with baseline platelet counts ≤75 × 109/L. Seven patients experienced platelet count increases ≥15 × 109/L. Mean hemoglobin levels remained stable over the treatment period. Two patients discontinued for adverse events: 1 for grade 4 retroperitoneal hemorrhage secondary to multiple and suspected pre-existing renal artery aneurysms and 1 for grade 4 thrombocytopenia. Conclusions: Results suggest that a low starting dose of ruxolitinib with escalation to 10 mg BID may be appropriate in myelofibrosis patients with low platelet counts. Trial registration. ClinicalTrials.gov: NCT01348490.
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U2 - 10.1186/1756-8722-6-81
DO - 10.1186/1756-8722-6-81
M3 - Article
C2 - 24283202
AN - SCOPUS:84886405838
VL - 6
JO - Journal of Hematology and Oncology
JF - Journal of Hematology and Oncology
SN - 1756-8722
IS - 1
M1 - 81
ER -