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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

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Front. Med.    2016, Vol. 10 Issue (4) : 437-443    https://doi.org/10.1007/s11684-016-0472-9
RESEARCH ARTICLE
Efficacy and safety of JAK inhibitor INC424 in patients with primary and post-polycythemia vera or post-essential thrombocythemia myelofibrosis in the Chinese population
Xin Du1,Daobin Zhou2()
1. Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
2. Department of Hematology, Peking Union Medical College Hospital, Beijing 100730, China
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Abstract

A phase II study (A2202) was performed to evaluate the efficacy and safety of JAK inhibitor ruxolitinib in 63 Chinese MF patients. Ruxolitinib was given twice a day (bid) at a starting dose of 15 mg (n=25) or 20 mg (n=38) based on a baseline platelet count. About 94.7% of the patients achieved a reduction in spleen size, 27.0% of which exhibited significant reduction (≥35%) at week 24. Significant improvement in debilitating constitutional symptoms, as assessed by MFSAF v2.0, was observed in patients treated with ruxolitinib. Ruxolitinib treatment was generally well tolerated by Chinese patients. Although the treatment was associated with an increase in certain adverse events (AEs) that were established as identified risks (anemia and thrombocytopenia), these AEs were considered manageable in this clinical setting. Ruxolitinib provided substantial reductions in splenomegaly and improvements in symptoms, and was well-tolerated by Chinese patients with MF.
Keywords JAK      ruxolitinib      Chinese patients      myelofibrosis     
Corresponding Author(s): Daobin Zhou   
Just Accepted Date: 12 October 2016   Online First Date: 17 November 2016    Issue Date: 01 December 2016
 Cite this article:   
Xin Du,Daobin Zhou. Efficacy and safety of JAK inhibitor INC424 in patients with primary and post-polycythemia vera or post-essential thrombocythemia myelofibrosis in the Chinese population[J]. Front. Med., 2016, 10(4): 437-443.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-016-0472-9
https://academic.hep.com.cn/fmd/EN/Y2016/V10/I4/437
Age (year)
Mean (SD) 54.3 (12.44)
Median (range) 55.0 (25–79)
Gender, n (%)
Female 31 (49.2)
Male 32 (50.8)
Type of MF, n (%)
PMF 49 (77.8)
PPV–MF 5 (7.9)
PET–MF 9 (14.3)
Time from diagnosis (year)
Mean (SD) 4.02 (4.960)
Median (range) 1.33 (0.1–20.3)
Palpable spleen size (cm) below costal margin
Mean (SD) 15.78 (7.041)
Median (range) 15.00 (6.0–45.0)
Spleen volume (cm3)
Mean (SD) 2421.9 (1024.25)
Median (range) 2236.0 (685–6076)
Baseline platelet count (K/ml)
Mean (SD) 281.81 (174.871)
Median (range) 227.00 (96.0–986.0)
Baseline hemoglobin count (K/ml)
Mean (SD) 10.32 (2.768)
Median (Range) 9.90 (4.7–17.9)
<10 g/dl, n (%) 34 (54.0)
≥10 g/dl, n (%) 29 (46.0)
Baseline circulating blasts (%)
Mean (SD) 0.97 (1.015)
Median (range) 1.00 (0.0–5.0)
ECOG PS, n (%)
0 34 (54.0)
1 26 (41.3)
2 3 (4.8)
≥3 0
Tab.1  Demographic and baseline characteristics (total n = 63)
Spleen volume Baseline (cm3) Week 24 (cm3) % Change from baseline at week 24
n 63 53 53
Mean (SD) 2421.9 (1024.25) 1731.8 (845.7) −26.94 (17.850)
Median 2236.0 1478.0 −25.11
Range 685?6076 345?3874 −72.4?5.3
Tab.2  Percentage change in spleen volume from baseline at week 24
Fig.1  Waterfall plot of percent change from baseline in spleen volume at week 24.
Fig.2  Kaplan–Meier estimates for time to first reduction (of at least 35%) in spleen volume among the responders.
PT All grades
n (%)		 Grade 3/4
n (%)
Any PT 59 (93.7) 33 (52.4)
Anemia 32 (50.8) 21 (33.3)
Platelet count decreased 22 (34.9) 5 (7.9)
Thrombocytopenia 14 (22.2) 1 (1.6)
Alanine aminotransferase increased 12 (19.0 0
Aspartate aminotransferase increased 10 (15.9) 0
Diarrhea 10 (15.9) 0
Neutrophil count decreased 8 (12.7) 1 (1.6)
Pyrexia 8 (12.7) 1 (1.6)
Upper respiratory tract infection 8 (12.7) 2 (3.2)
γ-glutamyltransferase increase 7 (11.1) 2( 3.2)
Lung infection 5 (7.9) 4 (6.3)
Weight increased 5 (7.9) 2 (3.2)
Abdominal distension 5 (7.9) 1 (1.6)
White blood cell count decreased 5 (7.9) 0
Activated partial thromboplastin time prolonged 4 (6.3) 0
Blood bilirubin increased 4 (6.3) 0
Blood iron increased 4 (6.3) 0
Blood urea increased 4 (6.3) 0
Tab.3  Frequent adverse events (at least 5% in all grades) in the study regardless of relation to the study drug
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[1] LIU Hongxing, TONG Chunrong, CAI Peng, GU Jiangying, LIN Yuehui, TENG Wen, WANG He, ZHANG Ying, ZHU Ping. Observation of a higher JAK2 V617F homozygous mutated clone in polycythemia vera compared to essential thrombocythemia[J]. Front. Med., 2008, 2(3): 309-313.
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