慢性骨髓性白血病(CML)的症狀
• 20-40% 毫無症狀 • 非特異性症狀:
– 容易倦怠 – 體重減輕 – 食慾不振、發燒
• 脾臟腫大: 腹脹、腹痛 • 抽血異常:
– 白血球過多 – 血小板過多 – 不成熟的白血球 – 可能有貧血的現象
治療反應
• 完全血液緩解:血球數目和正常人無異
• 染色體緩解:費城染色體的減少或消失
– 完全染色體緩解:0%
– 主要染色體緩解:0-35%
– 沒有染色體緩解:95%以上
• 基因緩解:利用抽血分子檢驗的方法,測量異常細胞減少的程度(微量疾病)
歐洲白血病團體制定的治療指引 (針對TKI)2013:
References: 1. Baccarani M, et al. Presented at the 4th international Congress on Leukemia Lymphoma Myeloma. Istanbul, Turkey. May 22-25 2013.
時間 理想 警告 失敗
診斷時 - High risk
CCA in Ph+ -
用藥後3個月 微量疾病
RT-PCR: -1
Minor CgR to 95% Ph+
and/or > 10%
No CHR
and/or 95% Ph+
用藥後6個月 微量疾病
RT-PCR: -2
< CCgR to minor CgR
and/or > 1 – 10%
< minor CgR
and/or > 10%
用藥後12個月 微量疾病
RT-PCR: -3
> 0.1 – 1%
(CCyR, no MMR)
> 1% Ph+
and/or > 1%
(No CCyR)
泰息安使用三個月的成績
Outcome at
5 Yrs, %
Treatment BCR-ABL Level at 3 Mos P Value
≤ 1% > 1% - ≤ 10% > 10%
PFS Nilotinib* 94.6 95.3 78.3 .0010
Imatinib 95.3 98.5 80.1 < .0001
OS Nilotinib* 95.7 97.6 81.9 .0007
Imatinib 95.3 99.2 79.5 < .0001
MR4.5 Nilotinib* 70.0 52.0 8.0 .0001
Imatinib 67.0 34.0 15.0 .0016
Saglio G, et al. ASH 2013. Abstract 92.
BCR-ABL level ≤ 10%IS at 3 mos higher for nilotinib (91%) vs imatinib (67%) independent of Sokal risk score
*300 mg BID.
• BCR-ABL ≤ 10%IS at 3 months higher for dasatinib (84%) vs imatinib (64%) independent of Sokal risk score.
柏萊使用三個月的成績
Cortes JE, et al. ASH 2013. Abstract 653.
ELN-Defined MR, % Dasatinib
(n = 259)
Imatinib
(n = 260)
At 3 mos
Optimal: BCR-ABL ≤ 10%IS
Warning: BCR-ABL > 10%IS
84
16
64
36
At 6 mos
Optimal: BCR-ABL ≤ 1%IS
Warning: BCR-ABL > 1% to 10%IS
Failure: BCR-ABL > 10%IS
69
19
11
49
34
17
At 12 mos
Optimal: BCR-ABL ≤ 0.1%IS
Warning: BCR-ABL > 0.1 to 1%IS
Failure: BCR-ABL > 1%IS
46
37
18
30
37
33
泰息安使用後進展到加速期/急性期的比率
• Rates of progression to AP/BC were lower with nilotinib vs imatinib when including all progressions occurring on study
• 2 new cases of progression to AP/BC after discontinuation of core treatment were observed between the 4-yr analysis and the current analysis
– 1 in the imatinib arm and 1 in the nilotinib 300 mg BID arm
– BCR-ABL > 10%IS at 3 mos for both patients
Imatinib 400 mg BID (n = 283) Nilotinib 300 mg BID (n = 282)
Nilotinib 400 mg BID (n = 281)
Saglio G, et al. ASH 2013. Abstract 92.
Pat
ien
ts (
n)
Progressions of Study
7.1% 3.5% 2.1%
P = .0588 P = .0047
25
20
15
10
5
0
20
10
6 New events in Yr 5
柏萊使用後進展到加速期/急性期的比率
n =
Pat
ien
ts (
n)
On Study Including Follow-up Beyond Discontinuation (ITT)*
14 (5.4%)
8(3.1%)
12
18
Dasatinib 100 mg QD Imatinib 400 mg QD
259
260
259
260 0
5
20
10
15
Cortes JE, et al. ASH 2013. Abstract 653.
Saglio G, et al. ASH 2013. Abstract 92. Used with permission.
泰息安使用後的基因緩解
100
80
60
40
20
0 2 1 4 3 5 6
Yrs Since Randomization
Pat
ien
ts W
ith
MM
R (
%)
Nilotinib 300 mg BID (n = 282) Nilotinib 400 mg BID (n = 281) Imatinib 400 mg QD (n = 283)
By 1 yr: By 4 yrs:
73% (P < .0001) ∆17% to 20%
56%
27%
By 5 yrs:
77% (P < .0001) ∆17%
60% 51% (P < .0001) ∆24% to 28%
0
55% (P < .0001)
76% (P < .0001)
77% (P < .0001)
柏萊使用後的基因緩解
MMR = major molecular response, BCR-ABL ≤0.1%
MMR 4-year
cumulative rates
Hasford Risk Score
Low Intermediate High
Dasatinib 90% 70% 65%
Imatinib 69% 63% 52%
With faster and deeper responses, dasatinib maintained higher MMR rates vs imatinib at year 4 across all risk groups
Dasatinib 100 mg QD
Imatinib 400 mg QD
0 12 Months
24 36 48 60
0
20
40
60
80
100 P<0.0001
% W
ith
MM
R
46%
23%
64%
46%
69%
55%
74%
60%
76%
63%
1.6-fold higher likelihood of achieving MMR with dasatinib; HR=1.55 (1.26-1.91)
試著停藥的STIM Study
N=100
STOP
Sustained CMR
for ≥ 2 years
Start Imatinib
CMR
Q- RT-PCR from peripheral
blood every month in the
first year and every 2
months thereafter
Five BCR–ABL
analyses by Q- RT-PCR
during these 2 years
Sixth datapoint
checked in
centralized
laboratory
Mahon FX et al. The Lancet Oncology, 2010;11(11):
1029-1035.
Molecular recurrence: positivity of BCR–ABL
transcript in Q-RT-PCR
confirmed by a second
analysis point indicating the
increase of one log in relation
to the first analysis point, at
two successive assessments,
or loss of MMR at one point.