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Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts

Moshe Talpaz1*, Ronald Paquette2, Lawrence Afrin3, Solomon I Hamburg4, Josef T Prchal5, Katarzyna Jamieson6, Howard R Terebelo7, Gregory L Ortega8, Roger M Lyons9, Ramon V Tiu10, Elliott F Winton11, Kavita Natrajan12, Olatoyosi Odenike13, David Claxton14, Wei Peng15, Peter O’Neill15, Susan Erickson-Viitanen15, Lance Leopold15, Victor Sandor15, Richard S Levy15, Hagop M Kantarjian16 and Srdan Verstovsek16

Author Affiliations

1 University of Michigan, Comprehensive Cancer Center, 1500 E Medical Center Dr, Ann Arbor MI 48109, USA

2 UCLA Division of Hematology/Oncology, Los Angeles, CA, USA

3 Medical University of South Carolina, Charleston, SC, USA

4 Tower Cancer Research Foundation, Beverly Hills, CA, USA

5 University of Utah School of Medicine, Salt Lake City, UT, USA

6 University of Iowa College of Medicine, Iowa City, IA, USA

7 Newland Medical Associates, Southfield, MI, USA

8 Mid-Florida Hematology & Oncology Associates, Orange City, FL, USA

9 Cancer Care Centers of South Texas/US Oncology, San Antonio, TX, USA

10 Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH, USA

11 Emory University School of Medicine, Atlanta, GA, USA

12 Georgia Regents University, Augusta, GA, USA

13 University of Chicago, Chicago, IL, USA

14 Penn State Hershey Cancer Institute, Hershey, PA, USA

15 Incyte Corporation, Wilmington, DE, USA

16 University of Texas MD Anderson Cancer Center, Houston, TX, USA

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Journal of Hematology & Oncology 2013, 6:81  doi:10.1186/1756-8722-6-81

Published: 29 October 2013



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.


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.


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.


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 NCT01348490.

Janus kinase inhibitor; Myelofibrosis; Phase II; Platelet count; Ruxolitinib; Spleen volume; Total symptom score