1) The document discusses the current treatment landscape for chronic myeloid leukemia (CML) in China, including the limited national insurance coverage of therapies. 2) Data is presented from a single center on response rates and outcomes for patients treated with imatinib or second-generation tyrosine kinase inhibitors, as well as transplant outcomes in the tyrosine kinase inhibitor era. 3) Therapeutic choices for CML patients are discussed based on financial constraints, with imatinib as the main first-line option and transplant playing a role for select patients who cannot afford long-term tyrosine kinase inhibitor therapy.

1. CML in China
Qian Jiang, MD
Peking University People's Hospital,
Peking University Institute of Hematology
2013-2-22

2. CML in China
江倩
北京大学 人民医院
北京大学 血液病研究所
2013-2-22

3. Outline
• Current status of CML in China
• TKI treatment for CML patients: experience
from single center
• Transplant in the TKI era: experience from
single center
• Therapeutic choices for CML patients based
on financial constraints

4. Outline
• Current status of CML in China
• TKI treatment for CML patients: experience
from single center
• Transplant in the TKI era: experience from
single center
• Therapeutic choices for CML patients based
on financial constraints

5. Incidence of CML
• Annual incidence: 0.4/100,000 population
• Median age at diagnosis: 40 years
• Male: Female = 1.4 - 2.3 : 1
• Disease phase at diagnosis:
- CP: 80% - 90%
- AP and BP: 10% - 20%
Kim DW, et al. Leuk Res. 2010;34:1459-71
Wang JX, et al. Zhonghua Xue Ye Xue Za Zhi. 2009;30:721-5.

6. National insurance coverage of CML
therapies in China
• Hydroxyurea: fully covered
• Interferon: partial covered
• Transplant: partial covered, ￥ 30,0000-
￥ 500,000
• Imatinib: not covered in the majority of regions
- partial covered in a few provinces and cities
- available through GIPAP, at least ￥ 70,000 each
year
• Dasatinib & Nilotinib: not covered
- available through access program, at least ￥ 90,000

7. Treatment Patterns
Asia CML Study Alliance (ACSA) developed a survey to assess current CML treatment
patterns in the Asia-Pacific region between Nov 2008 and April 2009.
Kim DW, et al. Leuk Res. 2010;34:1459-71

8. Number of patients who received
imatinib treatment by year
ECP
LCP
AP
BP
0
500
1000
1500
2000
2500
Casenumber
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
Year
Data from CCF

9. Number of patients who received
2nd
generation TKIs treatment by year
Nilotinib
Dasatinib
• Dasatinib and nilotinib were approved as the second-line options
after imatinib failure in China.
• Most patients received 2nd
generation TKIs in advanced phase.
• 2nd
TKIs were used as a first-line therapy only for clinical trials.
Data from CCF & BMS

10. Casenumber
Data from Chinese Hematopoietic Stem Cell Transplantation Register Group
Transplantation is preferred for CML patients with TKI failure, in
advanced phase, or those who can not afford TKI treatment.
Number of patients who underwent
transplantat by year

11. Outline
• Current status of CML in China
• TKI treatment for CML patients: experience
from single center
• Transplant in the TKI era: experience from
single center
• Therapeutic choices for CML patients based
on financial constraints

12. Imatinib therapy for newly diagnosed
patients in chronic phase: response
rates
Estimated rate
at 12 months at 48 months
CCR n=172 86.0% 93.7%
MMR n=165 34.1% 72.1%
CMR n=165 12.2% 49.7%
Median follow-up was 34 months (range, 4-118 months).
Data from Peking University People's Hospital

13. Total n=172 Estimated rate at 48 months
EFS event n=20 87.7%
PFS AP/BP n=11 93.2%
OS dead n=4 81.9%
98.8% (considering only CML related deaths)
• Median time to event was 9 months.
• Median time to AP/BP was 12 months.
• Median time to dead was 7 months.
ProbabilityofEFS, Imatinib therapy for newly diagnosed
patients in chronic phase: EFS, PFS and OS
Data from Peking University People's Hospital

14. Total n=56 At 10 years
EFS event n=21 61.0%
PFS AP/BP n=8 84.8%
OS dead n=6 87.8%
90.1% (considering only CML related deaths)
Imatinib therapy for interferon-failure
patients in chronic phase: EFS, PFS and OS
ProbabilityofEFS,P
Months
Data from Peking University People's Hospital

15. Imatinib versus nilotinib for newly diagnosed
patients in chronic phase: CCR rate
28 27 27
31 31 30
P=0.003 P=0.039
Data from Peking University People's Hospital

16. 3m 6m 12m
P=0.055 P=0.027 P=0.003
BCR-ABL mRNA
reduction
Imatinib versus nilotinib for newly
diagnosed patients in chronic phase:
molecular response
Data from Peking University People's Hospital

17. n=5 n=2
n=8 n=3
Imatinib versus nilotinib for newly
diagnosed patients in chronic phase:
event and progression
The superior rate of responses has not
yet translated into improvements in
EFS, PFS and OS.
Data from Peking University People's Hospital

18. Dasatinib as a second- or third-line
therapy for imatinib-failure patients
CP n=27
AP n=18
BP n=40
CP n=27
AP n=16
BP n=27
Data from Peking University People's Hospital

19. Outline
• Current status of CML in China
• TKI treatment for CML patients: experience
from single center
• Transplant in the TKI era: experience from
single center
• Therapeutic choices for CML patients based
on financial constraints

20. Imatinib versus transplant for patients
with CP CML <1 year after diagnosis:
Flow chart of study
348 pts with CP CML <55 years old prospectively assigned to
receive imatinib or an HLA-identical sibling transplant from April,
2001 to March, 2010.
Jiang Q et al. ASH 2011 Abstract No. 162

21. Imatinib therapy was associated with better
outcomes than transplant in patients with
CP CML <1 year after diagnosis
•No 5-year TRM in the imatinib cohort compared to 17% in the
transplant cohort.
•5-year CIFs of progression were comparable in both cohorts.
•More MMR and CMR were in the transplant cohort.
RR=3.62
(95% CI, 1.95–6.72)
P<0.0001
RR=5.30
(95% CI, 2.40–11.71)
P<0.0001
RR=41.84
(95% CI, 5.66–309)
P<0.0001)
EFS PFS Survival
Jiang Q et al. ASH 2011 Abstract No. 162

22. Imatinib versus transplant for previously
imatinib-untreated AP CML patients
0 20 40 60 80 100 120
0
20
40
60
80
100
Imatinib n=87
Allo-HSCT n=45
P=0.035
Months
Event-freesurvival
EFS rate at 6 years
71.8%
39.2%
Jiang Q, et al. Blood. 2011. 17;117:3032-40.
0 20 40 60 80 100 120
0
20
40
60
80
100
Imatinib n=87
Allo-HSCT n=45
P=0.023
Months
Overallsurvival
OS rate at 6 years
83.3%
51.4%
0 20 40 60 80 100 120
0
20
40
60
80
100
Imatinib n=83
Allo-HSCT n=44
P=0.000
Months
Progression-freesurvival
PFS rate at 6 years
95.2%
48.3%
A cohort study was designed to
compare the outcomes of imatinib vs.
allo-HSCT for AP CML from April 2001
to Sep 2008, 132 pts were enrolled.

23. • CML duration ≥ 12 months
• hemoglobin < 100 g/L
• peripheral blood blasts ≥ 5%
Independent adverse prognostic factors
prior to treatment for both OS and PFS
In an attempt to determine whether choice of therapy contributed to the
survival differences, we categorized the entire cohort into 3 groups:
- low-risk (no factor): n = 40
- intermediate-risk (any factor): n = 59
- high-risk (at least two factors): n = 33
Jiang Q, et al. Blood. 2011. 17;117:3032-40.

24. 0 20 40 60 80 100 120
0
20
40
60
80
100
Imatinib n=17
Allo-HSCT n=23
P=0.898
Months
Event-freesurvival
0 20 40 60 80 100 120
0
20
40
60
80
100
Imatinib n=17
Allo-HSCT n=23
P=0.114
Months
Overallsurvival
EFS, OS and PFS in low-risk
AP CML patients by therapy
Absence of significant differences
between the two groups.
Jiang Q, et al. Blood. 2011. 17;117:3032-40.

25. 0 20 40 60 80 100 120
0
20
40
60
80
100
Imatinib n=43
Allo-HSCT n=16
P=0.788
Months
Event-freesurvival
0 20 40 60 80 100 120
0
20
40
60
80
100
Imatinib n=43
Allo-HSCT n=16
P=0.773
Months
Overallsurvival
EFS, OS and PFS in intermediate-risk
AP CML patients by therapy
• EFS & OS did not differ in terms of
therapy mode.
• More relapse developed in the
imatinib group.
Jiang Q, et al. Blood. 2011. 17;117:3032-40.

26. 0 20 40 60 80 100 120
0
20
40
60
80
100
Imatinib n=27
Allo-HSCT n=6
P=0.030
Months
Event-freesurvival
0 20 40 60 80 100 120
0
20
40
60
80
100
Imatinib n=27
Allo-HSCT n=6
P=0.008
Months
Overallsurvival
EFS, OS and PFS in high-risk
AP CML patients by therapy
Allo-HSCT was significantly superior
to imatinib.
Jiang Q, et al. Blood. 2011. 17;117:3032-40.

27. Conclusions
• Allo-HSCT is superior to imatinib, conferring
significant survival advantages to high- and
intermediate-risk patients.
• We recommend those patients receive an early
transplant after achieving a second CP with
imatinib.
Jiang Q, et al. Blood. 2011. 17;117:3032-40.

28. Conclusions (Cont’d)
• Outcomes of imatinib and allo-HSCT were
equally good in low-risk patients with CML in
AP.
• For low-risk patients, imatinib may remain the
primary option so long as MRD is carefully
monitored, and allo-HSCT should be
considered if there is evidence of imatinib
resistance.
Jiang Q, et al. Blood. 2011. 17;117:3032-40.

29. TKIs versus transplant for previously TKI-
untreated BP CML patients by therapy
OS
EFS
EFS
OS
PFS
Allo-HSCT was significantly superior
to TKIs.
Data from Peking University People's Hospital

30. Outline
• Current status of CML in China
• TKI treatment for CML patients: experience
from single center
• Transplant in the TKI era: experience from
single center
• Therapeutic choices for CML patients based
on financial constraints

31. What will be the first option for CP CML
patients in China?
• TKIs, a life-long therapy, are used mainly
through partially paid patient access program.
• 2nd
generation TKIs are more expensive than
imatinib, not covered by insurance and
approved by SFAD only for a second-line
therapy for imatinib-failure patients.
• So, imatinib will be the mainstay choice as a
first-line option for CML.

32. What is the role of transplant
in the TKI era for CML in China?
• Transplant offers the possibility of a cure with
less cost than TKIs therapy.
• One-off transplant versus the expense of
lifetime TKI therapy.
• So, transplant perhaps will remain a first
choice for a few young CP CML patients with
an HLA-identical donor and a second-line
option following imatinib for those who can’t
afford a long-term 2nd
generation TKI therapy.

33. What is our next move?
• To find ways to make TKIs more widely
available to more CML patients and increase
accessibility of affordable therapeutic
approaches.
• To improve CML management according to
international guidelines by routine cytogenetic
and molecular monitoring.
• To identify early signs of resistance to TKIs and
enable a timely switch to alternative therapies.