Patient perspective on TKI treatment and monitoring in CML. Qian Jiang

1. Real-World Analysis of Tyrosine Kinase Inhibitor
Treatment and Monitoring in Patients with Chronic
Myeloid Leukemia in China: from Patients’ Perspective
Qian Jiang, M.D.
Peking University People's Hospital, Beijing, China

2. Introduction

3. Epidemiology of CML in China
• Annual incidence of CML:
0.39-0.55 per 100,000
• Median age at diagnosis:
45-50 year old
• Male to female ratio:
1.5:1
Wang AH, et al. J Exp Clin Cancer Res. 2010, 3;29:20.
Wang JX, et al. Zhonghua Xue Ye Xue Za Zhi. 2009, 30:721-725

4. CML Treatment Pattern 6 Years Ago
Wang JX, et al. Zhonghua Xue Ye Xue Za Zhi. 2009, 30:721-725
Kim DW, et al. Leuk Res. 2010, 34:1459-71.
n=1824

5. Number of Patients on TKIs
0
500
1000
1500
2000
2500
Casenumber
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
Year
0
100
200
300
400
500
Casenumber
2010 2011 2012
Year
系列1
系列2
TKI No. of patients
Glivec 30,000
Tasigna 3,400
Sprycel 700
• Imatinib was approved as the first-line
TKI, Dasatinib and nilotinib, as the
second-line options
• TKIs are reimbursed in some provinces.
• Partial payment for Patient Assistance
Program (PAP) is the mainstay of
access to TKIs.
• Up to 2012, the number of patients on
original TKIs:
Data from CCF & CFC

6. TKIs available in Developed Countries

7. TKIs available in China
Chinese generic imatinib Chinese generic
dasatinib
Indian generic
TKIs

8. Brand name
PAP
Model
(mo.)
Payment
without
PAP/Year
（$）
Payment
with
PAP/Year
（$）
Payment
with PAP &
Reimbursement
/Year
（$）
Approved
Indication
Glivec 3+9 44,500 11,100 3,300 First line
Tasigna 3+12 56,200-69,700 11,200-13,900 3,300-4,100 Second line
Sprycel 3+9 61,100 15,300 6,100-18,300 Second line
Chinese generic imatinib NA 5,800 1,700 First line
Chinese generic dasatinib NA 8,800 Second line
Indian generic
Imatinib/dasatinib
NA 500-2,400 NA
TKI Payment

9. Study Design
• This was an open-label and non-interventional, cross-sectional study
• Physicians and New Sunshine Charity Foundation designed the study, collected the
questionnaires and analyzed the data
• From May to October, 2014, anonymous questionnaires were distributed to adults
with CML receiving TKI treatment in China via the Internet and in printed copies at
patient advocacy groups, PAP pharmacies and the out-patient clinics at Peking
University People's Hospital
• The study was approved by the ethics committee of Peking University People‘s
Hospital
• The questionnaire focused on demographics, disease-related variables before
starting the TKI or TKI(s) given, response and tolerance, monitoring, duration of TKI
therapy, annual out-of-pocket expense, and major impediment to receiving TKI

10. Results

11. Demographics & Disease-related Variables
Before TKI Treatment
• 1038 questionnaires were collected
• 949 questionnaires were evaluable including 358 electronic copies (38%) and 591 printed copies (62%)
Variable Value
Gender, n (%)
Male 557 (58.0)
Female 357 (37.1)
Declined 47 (4.9)
Age, y median (range) 41 (18-88)
Household register, n (%)
Urban 629 (65.5)
Rural 239 (24.9)
Declined 93 (9.7)
Educational level, n (%)
Secondary school and below 411 (42.8)
University and above 456 (47.5)
Declined 94 (9.8)
First diagnosis time, y median (range) 2011 (1980-2014)
Disease phase at diagnosis, n (%)
CP 899 (93.5)
AP 49 (5.1)
BP 10 (1.0)
Declined 3 (0.3)
Treatment Prior to TKI, n (%)
Hydroxyurea (more than 1 mo) 298 (31.0)
Interferon (more than 6 mo) 110 (11.4)
Chemotherapy 41 (4.3)
Transplant 7 (0.7)
Chinese traditional medicine 140 (14.6)

12. The Distribution of Patients’ Interval from the
Diagnosis to TKI Treatment (I)
＜1y
74.5%
1y-2y
12.8%
2y-3y
3.2%
3y-5y
4.1%
＞5y
5.5%

13. The Distribution of Patients’ Interval from the
Diagnosis to TKI Treatment (II)
Time when patients
began TKI treatment
0.0%
20.0%
40.0%
60.0%
80.0%
100.0%
2001* 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014**
＞5y
3-5y
2-3y
1-2y
＜1y
n 20 8 2 11 24 29 39 61 79 66 140 183 193 106

14. The Distribution of TKIs Used (I)
Tasgina
10.6%
Glivec
66.1%
Chinese generic
dasatnib
0.7%
Chinese generic
imatinib
6.4%
Others
0.6%
Sprycel
4.2%
Indian generic
imatinib
11.2%
Indian generic
dasatinib
0.1%
Imatinib 83%; Branded drugs 81%; Nilotinib or dasatinib as initial therapy on clinical trials 15%

15. The Distribution of TKIs Used (II)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Branded
drugs
Generic
drugs
n 20 8 2 11 24 29 39 61 79 66 140 183 193 106
Time when patients
began TKI treatment
Subjects receiving generics had a longer interval from the diagnosis to TKI treatment than those on
branded drugs: 55/240 (23%) vs. 120/703 (17); P=0.044

16. TKI Responses
• Median TKI treatment duration was 3 years (range, <1-13
years)
• 708 of 834 respondents (85%) achieved CCyR
• 497 of 859 respondents (46%) achieved CMR

17. Impact of TKI Treatment
Adverse Effects on Quality of Life
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
44.1% 38.6%
32.5%
19.6% 19.0% 15.0% 12.4%
22.6%
1
30.1%
2
21.5%
3
28.7%
4
9.3%
5
10.4%
QOL from 1–5
(1 being “no impact”,
5 being “high impact”)

18. Annual Out-of-pocket TKI Cost (I)
Free
17.1%
<＄4,000
17.9%
＄4,000-＄8,000
8.1%
＄8,000-＄12,000
46.3%
≥＄12,000
10.6%
Multivariate analyses showed that urban population (HR=2.0, P=0.004), increasing age
(HR=1.6, P=0.040), starting TKI therapy within 1 year from diagnosis (HR=0.6, P=0.026),
receiving 2nd generation TKI (HR=3.7, P=0.001) and branded drug (HR=37.0, P<0.001) were
associated with annual out-of-pocket expenses > $8,000 USD

19. Annual Out-of-pocket TKI Cost (II)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
＞＄12,000
＄8,000-＄12,000
＄4,000-＄8,000
＜＄4,000
free
n 20 8 2 11 24 29 39 61 79 66 140 183 193 106
Time when patients
began TKI treatment

20. Obstacles to Receiving TKI Therapy
Satisfied
1.7%
Side effect
17.2%
Heavy financial
burden
61.8%
Unsatisfied
treatment
outcome
7.4%
Inconvenient PAP
drug access
9.6%
Others
2.3%
Others: 20 respondents reported it was inconvenient to get or take the drug, worries about
disease progression, future drug side effects and pressure from their family and/or society

21. Monitoring During TKI Treatment
• 795 respondents (84%) had done ≥1 CBC, 406 (43%) had ≥1 bone marrow
cytogenetic analysis and 795 (91%) had ≥1 BCR-ABL level test by Q-PCR.
• The frequency of regular visit to clinic:
Irregular
detection
4.2% Every month
29.1%
Every 3 months
38.1%
Every 6 months
23.6%
Every 12 months
5.0%

22. The Frequency of Molecular Monitoring
Irregular detection
13.6%
Never
10.7%
Every 3 months
32.8%
Every 6 months
33.5%
Every 12 months
9.4%

23. Reasons of Never and Irregular Molecular
Monitoring (n=106)
No cost sharing by
medical insurance
18.9%
No necessity for
monitoring
10.4%
No eligible
laboratory in
nearby
hospitals
10.4%
No requirement by
physicians
60.4%
Multivariate analysis showed increasing age (HR=2.0, P<0.001), rural households (HR=2.0,
P<0.001), shorter interval from diagnosis to TKI treatment (HR=1.5, P=0.035), briefer TKI therapy
(HR=3.5, P<0.001), and use of generics (HR=3.0, P<0.001) were associated with never or
irregular molecular monitoring

24. Conclusions (I)
• The current survey reflected the real-world of CML treatment and
monitoring patterns in China from patients’ perspective
• More than 70% of the respondents received a TKI within 1 year
from diagnosis
• Imatinib is the most commonly used TKI
• The 2nd generation TKIs are mainly used as a second- or third-line
therapy
• Branded (non-generic) TKIs are still the mainstream

25. Conclusions (II)
• Majority of the respondents achieved optimal response and were
well tolerate on TKI
• Financial burden is the biggest obstacle to receive TKI therapy
• One-third of the respondents did not performed regular
monitoring on TKI
• It is expected to lower the prices of anticancer drugs, expand the
coverage of medical insurance and develope generic drugs
• Standard molecular monitoring needs to be highlighted

26. Thank You for Your Kind Attention!
jiangqian@medail.com.cn