EXPAND, a dose-finding study of ruxolitinib in patients with myelofibrosis and low platelet counts: 48-week follow-up analysis

被引:40
作者
Vannucchi, Alessandro M. [1 ]
te Boekhorst, Peter A. W. [2 ]
Harrison, Claire N. [3 ]
He, Guangsheng [4 ]
Caramella, Marianna [5 ]
Niederwieser, Dietger [6 ]
Boyer-Perrard, Francoise [7 ]
Duan, Minghui [8 ]
Francillard, Nathalie [9 ]
Molloy, Betty [10 ]
Wroclawska, Monika [10 ]
Gisslinger, Heinz [11 ]
机构
[1] Univ Florence, Azienda Osped Univ Careggi, Ctr Res & Innovat Myeloproliferat Neoplasms, Florence, Italy
[2] Erasmus MC, Rotterdam, Netherlands
[3] Guys & St Thomas NHS Fdn Trust, Guys Hosp, London, England
[4] Nanjing Med Univ, Hosp 1, Nanjing, Jiangsu, Peoples R China
[5] ASST Grande Osped Metropolitano, Milan, Italy
[6] Univ Leipzig, Dept Hematol & Med Oncol, Leipzig, Germany
[7] CHU Angers, Angers, France
[8] Peking Union Med Coll Hosp, Beijing, Peoples R China
[9] Novartis Pharma SAS, Rueil Malmaison, France
[10] Novartis AG, Basel, Switzerland
[11] Med Univ Vienna, Dept Med 1, Div Hematol & Hemostaseol, Vienna, Austria
关键词
SYMPTOM ASSESSMENT FORM; QUALITY-OF-LIFE; AVAILABLE THERAPY; SCORING SYSTEM; JAK2; INHIBITOR; OPEN-LABEL; EFFICACY; SAFETY; DEFINITION; INCB018424;
D O I
10.3324/haematol.2018.204602
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
EEXPAND (phase Ib, dose-finding study) evaluated the starting dose of ruxolitinib in patients with myelofibrosis with baseline platelet counts of 50-99x10(9)/L. The study consisted of dose-escalation and safety-expansion phases. Based on the baseline platelet counts, patients were assigned to stratum 1 (75-99x10(9)/L) or stratum 2 (50-74x10(9)/L), with the primary objective of determining the maximum safe starting dose (MSSD); key secondary objectives included safety and efficacy. At week 48 data cutoff (stratum 1, n=44; stratum 2, n=25), 24.6% (17 out of 69) of patients were still receiving treatment. The MSSD was established as ruxolitinib 10 mg twice daily in both strata. Thrombocytopenia [grade 4 (stratum 1, n=1; stratum 2, n=2)] was the only reported dose-limiting toxicity (study drug related) at 10 mg twice daily. In the MSSD cohort (stratum 1, n=20; stratum 2, n=18), adverse events (regardless of study drug relationship) led to treatment discontinuation in 15.0% and 33.3% of patients in stratum 1 and stratum 2, respectively, and dose adjustment/interruption in 45.0% and 66.7% of patients in stratum 1 and stratum 2, respectively. Three cases of on-treatment deaths were reported at the MSSD. Spleen response was achieved at week 48 in 33.3% and 30.0 % of patients in stratum 1 and stratum 2, respectively. Improvements in the Total Symptom Score were also observed. In this study, ruxolitinib demonstrated acceptable tolerability in both the strata at the MSSD of 10 mg twice daily.
引用
收藏
页码:947 / 954
页数:8
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