Evaluation of the dose and efficacy of ruxolitinib in Japanese patients with myelofibrosis.

Abstract

Ruxolitinib, a potent JAK1/JAK2 inhibitor, improved splenomegaly and myelofibrosis-associated symptoms and prolonged survival compared with placebo and best available therapy in the phase 3 COMFORT studies. Although cytopenias were the most common adverse events associated with ruxolitinib treatment, a COMFORT-I analysis showed that they were managed effectively with dose modifications, without a negative impact on the efficacy of ruxolitinib. Subsequently, studies A2202 and AJP01 showed that ruxolitinib is an effective treatment for Japanese patients with myelofibrosis. We conducted a pooled analysis of these two studies (N = 81) to evaluate the association between ruxolitinib dose and changes in spleen volume or symptoms in Japanese patients. Most patients began treatment at 15 or 20 mg twice daily (BID); 70% received a final titrated dose ≥ 10 mg BID. Overall, 91% of patients exhibited spleen volume reductions; patients with final titrated doses ≥ 10 mg BID had larger spleen volume reductions. Similarly, 83% of patients showed improvements in symptom scores; those with a final titrated dose of 20 or 25 mg BID had the greatest reductions. Consistent with COMFORT-I, this pooled analysis indicates that, despite dose adjustments, ruxolitinib provides spleen and symptom control in Japanese patients, with higher doses associated with better responses.

• Authors: Keita Kirito, Shinichiro Okamoto, Kohshi Ohishi, Tetsuzo Tauchi, Hiroshi Handa, Shigeki Saito, Katsuto Takenaka, Kazuya Shimoda, Kenji Oritani, Koichi Akashi, Hikaru Okada, Taro Amagasaki, Kazuyuki Suzuki, Toshio Yonezu, Norio Komatsu
• Journal: International journal of hematology (Int J Hematol) Vol. 107 Issue 1 Pg. 92-97 (Jan 2018) ISSN: 1865-3774 [Electronic] Japan
• PMID: 28986762 (Publication Type: Journal Article)

Chemical References

• Janus Kinase Inhibitors
• Nitriles
• Pyrazoles
• Pyrimidines
• ruxolitinib

Topics

• Adult
• Aged
• Aged, 80 and over
• Asian People
• Clinical Studies as Topic
• Clinical Trials, Phase I as Topic
• Clinical Trials, Phase III as Topic
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Humans
• Janus Kinase Inhibitors (administration & dosage, adverse effects)
• Male
• Middle Aged
• Multicenter Studies as Topic
• Nitriles
• Primary Myelofibrosis (drug therapy)
• Pyrazoles (administration & dosage, adverse effects)
• Pyrimidines
• Treatment Outcome