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CML in China
Qian Jiang, MD
Peking University People's Hospital,
Peking University Institute of Hematology
2013-2-22
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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
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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
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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
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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;34:1459-71Wang JX, et al. Zhonghua Xue Ye Xue Za Zhi. 2009;30:721-5.
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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
each year
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Treatment PatternsAsia 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
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Number of patients who received imatinib treatment by year
ECPLCPAPBP
0
500
1000
1500
2000
2500
Case n
um
ber
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
Year
Data from CCF
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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
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Ca
se
nu
mb
er
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
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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
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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
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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.
Pro
bab
ilit
y o
f E
FS
, P
FS
an
d O
SImatinib therapy for newly diagnosed
patients in chronic phase: EFS, PFS and OS
Data from Peking University People's Hospital
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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
Pro
bab
ilit
y o
f E
FS
, P
FS
an
d O
S
MonthsData from Peking University People's Hospital
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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
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3m 6m 12m
P=0.055 P=0.027 P=0.003BCR-ABL mRNA
reductionBCR-ABL mRNA
reduction
Imatinib versus nilotinib for newly diagnosed patients in chronic phase:
molecular response
Data from Peking University People's Hospital
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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
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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
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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
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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
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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
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Imatinib versus transplant for previously imatinib-untreated AP CML patients
0 20 40 60 80 100 1200
20
40
60
80
100
Imatinib n=87
Allo-HSCT n=45
P=0.035
Months
Eve
nt-
free
su
rviv
al
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 1200
20
40
60
80
100
Imatinib n=87
Allo-HSCT n=45
P=0.023
Months
Ove
rall
surv
ival
OS rate at 6 years
83.3%
51.4%
0 20 40 60 80 100 1200
20
40
60
80
100
Imatinib n=83
Allo-HSCT n=44
P=0.000
Months
Pro
gre
ssio
n-f
ree
surv
ival
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.
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• 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.
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0 20 40 60 80 100 1200
20
40
60
80
100
Imatinib n=17
Allo-HSCT n=23
P=0.898
Months
Eve
nt-
free
su
rviv
al
0 20 40 60 80 100 1200
20
40
60
80
100
Imatinib n=17
Allo-HSCT n=23
P=0.114
Months
Ove
rall
surv
ival
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.
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0 20 40 60 80 100 1200
20
40
60
80
100
Imatinib n=43
Allo-HSCT n=16
P=0.788
Months
Eve
nt-
free
su
rviv
al
0 20 40 60 80 100 1200
20
40
60
80
100
Imatinib n=43
Allo-HSCT n=16
P=0.773
Months
Ove
rall
surv
ival
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.
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0 20 40 60 80 100 1200
20
40
60
80
100
Imatinib n=27
Allo-HSCT n=6
P=0.030
Months
Eve
nt-
free
su
rviv
al
0 20 40 60 80 100 1200
20
40
60
80
100
Imatinib n=27
Allo-HSCT n=6
P=0.008
Months
Ove
rall
surv
ival
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.
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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.
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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.
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TKIs versus transplant for previously TKI-untreated BP CML patients by therapy
OS
EFSEFS
OS
PFS
Allo-HSCT was significantly superior
to TKIs.
Data from Peking University People's Hospital
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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
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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.
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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.
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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.