Evaluation of the dose and efficacy of ruxolitinib in Japanese patients with myelofibrosis
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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.
KeywordsMyelofibrosis JAK inhibitor Ruxolitinib Japanese patients
Editorial assistance was provided by Karen Chinchilla, PhD, of ArticulateScience LLC and was funded by Novartis Pharma KK.
Compliance with ethical standards
Conflict of interest
KK reports personal fees from Novartis Pharma KK, during conduct of the study. K. Shimoda reports grants and personal fees from Novartis Pharma KK, outside the submitted work. K. Oritani reports personal fees for lectures and scholarship contributions from Novartis Pharma KK, outside the submitted work. HO, TA, K Suzuki, and TY are employees of Novartis Pharma KK. SO, K. Ohishi, TT, HH, SS, KT, KA, and NK have no conflicts of interest to disclose.
- 10.Rumi E, Pietra D, Guglielmelli P, Bordoni R, Casetti I, Milanesi C, et al. Acquired copy-neutral loss of heterozygosity of chromosome 1p as a molecular event associated with marrow fibrosis in MPL-mutated myeloproliferative neoplasms. Blood. 2013;121(21):4388–95.CrossRefPubMedPubMedCentralGoogle Scholar
- 22.Mesa RA, Gotlib J, Gupta V, Catalano JV, Deininger MW, Shields AL, et al. Effect of ruxolitinib therapy on myelofibrosis-related symptoms and other patient-reported outcomes in COMFORT-I: a randomized, double-blind, placebo-controlled trial. J Clin Oncol. 2013;31(10):1285–92.CrossRefPubMedPubMedCentralGoogle Scholar
- 24.Vannucchi AM, Kantarjian HM, Kiladjian JJ, Gotlib J, Cervantes F, Mesa RA, et al. A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase 3 trials of ruxolitinib for the treatment of myelofibrosis. Haematologica. 2015;100(9):1139–45.CrossRefPubMedPubMedCentralGoogle Scholar