Transcript EFS, PFS and OS - ASIA-PACIFIC HEMATOLOGY CONSORTIUM

CML in China
Qian Jiang, MD
Peking University People's Hospital,
Peking University Institute of Hematology
2013-2-22
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
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
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
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.
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
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
Number of patients who received
imatinib treatment by year
2500
Case number
2000
1500
1000
500
0
2003
100
80
60
%
40
20
0
2004
2005
2006
2007
2008
2009
2010
2011
2012
Year
2009
2010
2011
Year
2012
ECP
系列1
LCP
系列2
系列3
AP
系列4
BP
Data from CCF
Number of patients who received
2nd generation TKIs treatment by year
Case number
500
400
300
200
Nilotinib
系列1
系列2
Dasatinib
100
0
2010
2011
2012
Year
• 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
Case number
Number of patients who underwent
transplantat by year
300
200
100
0
2007. 7-2008. 6
2008. 7-2009. 6
2009. 7-2010. 6
Year
Transplantation is preferred for CML patients with TKI failure, in
advanced phase, or those who can not afford TKI treatment.
Data from Chinese Hematopoietic Stem Cell Transplantation Register Group
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
Imatinib therapy for newly diagnosed
patients in chronic phase: response rates
Median follow-up was 34 months (range, 4-118 months).
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%
Data from Peking University People's Hospital
Probability of EFS, PFS and OS
Imatinib therapy for newly diagnosed
patients in chronic phase: EFS, PFS and OS
•
Median time to event was 9 months.
•
Median time to AP/BP was 12 months.
•
Median time to dead was 7 months.
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)
Data from Peking University People's Hospital
Probability of EFS, PFS and OS
Imatinib therapy for interferon-failure
patients in chronic phase: EFS, PFS and OS
EFS
PFS
OS
Total n=56
At 10 years
event n=21
61.0%
AP/BP n=8
84.8%
dead n=6
87.8%
90.1% (considering only CML related deaths)
Months
Data from Peking University People's Hospital
Imatinib versus nilotinib for newly diagnosed
patients in chronic phase: CCR rate
P=0.003
P=0.039
100.00%
80.00%
88.90%
71.40%
77.80%
73.30%
51.60%
60.00%
32.30%
40.00%
20.00%
0.00%
Nilotinib
Imatinib
3m
6m
12m
28
27
27
31
31
30
Data from Peking University People's Hospital
Imatinib versus nilotinib for newly
diagnosed patients in chronic phase:
molecular response
BCR-ABL mRNA
reduction
P=0.055
P=0.027
P=0.003
3m
6m
12m
1
0
-1
-2
-3
-4
Nilotinib
Imatinib
-5
Data from Peking University People's Hospital
Imatinib versus nilotinib for newly
diagnosed patients in chronic phase:
event and progression
100%
80%
60%
40%
The superior rate of responses has not
yet translated into improvements in EFS,
PFS and OS.
25.80%
17.90%
7.14%
20%
0%
Nilotinib
Imatinib
Event
9.68%
Progression
n=5
n=2
n=8
n=3
Data from Peking University People's Hospital
Dasatinib as a second- or third-line
therapy for imatinib-failure patients
100
HR
CHR
MCR
CCR
MMR
80
%
60
40
20
0
CP n=27
AP n=16
BP n=27
CP
AP
CMR
BP
CP n=27
AP n=18
BP n=40
Data from Peking University People's Hospital
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
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
Imatinib therapy was associated with better
outcomes than transplant in patients with
CP CML <1 year after diagnosis
EFS
RR=3.62
(95% CI, 1.95–6.72)
P<0.0001
PFS
RR=5.30
(95% CI, 2.40–11.71)
P<0.0001
Survival
RR=41.84
(95% CI, 5.66–309)
P<0.0001)
•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.
Jiang Q et al. ASH 2011 Abstract No. 162
Progression-free survival
Imatinib versus transplant for previously
imatinib-untreated AP CML patients
Overall survival
100
80
60
P=0.023
40
OS rate at 6 years
Allo-HSCT n=45
83.3%
Imatinib n=87
51.4%
20
0
0
Event-free survival
100
20
40
60
80
100
100
80
60
P=0.000
PFS rate at 6 years
40
95.2%
Allo-HSCT n=44
20
Imatinib
48.3%
n=83
0
0
20
40
60
80
100
120
Months
120
Months
80
60
P=0.035
40
EFS rate at 6 years
Allo-HSCT n=45
Imatinib n=87
20
71.8%
39.2%
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.
0
0
20
40
60
Months
80
100
120
Jiang Q, et al. Blood. 2011. 17;117:3032-40.
Independent adverse prognostic factors
prior to treatment for both OS and PFS
• CML duration ≥ 12 months
• hemoglobin < 100 g/L
• peripheral blood blasts ≥ 5%
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.
Progression-free survival
EFS, OS and PFS in low-risk
AP CML patients by therapy
Absence of significant differences
between the two groups.
Overall survival
100
Event-free survival
100
80
100
80
60
P=0.365
40
Allo-HSCT n=23
Imatinib n=16
20
0
0
60
20
40
60
80
100
Months
P=0.114
40
Allo-HSCT n=23
Imatinib n=17
20
0
80
0
20
40
60
80
100
120
Months
60
P=0.898
40
Allo-HSCT n=23
20
Imatinib
n=17
0
0
20
40
60
Months
80
100
120
Jiang Q, et al. Blood. 2011. 17;117:3032-40.
120
EFS, OS and PFS in intermediate-risk
AP CML patients by therapy
Progression-free survival
• EFS & OS did not differ in terms of
therapy mode.
• More relapse developed in the
imatinib group.
Overall survival
100
Event-free survival
100
80
100
80
60
P=0.047
40
Allo-HSCT n=15
Imatinib n=43
20
0
0
20
40
60
80
100
Months
60
P=0.773
40
Allo-HSCT n=16
Imatinib n=43
20
80
0
0
60
20
40
60
80
100
120
Months
P=0.788
40
Allo-HSCT n=16
Imatinib n=43
20
0
0
20
40
60
Months
80
100
120
Jiang Q, et al. Blood. 2011. 17;117:3032-40.
120
100
Overall survival
P=0.008
80
60
Allo-HSCT n=6
Imatinib n=27
40
20
Progression-free survival
EFS, OS and PFS in high-risk
AP CML patients by therapy
100
P=0.006
80
60
Allo-HSCT n=6
Imatinib n=24
40
20
0
0
20
40
60
80
100
120
Months
0
0
20
40
60
80
100
120
Months
Event-free survival
100
P=0.030
Allo-HSCT was significantly superior
to imatinib.
80
60
40
Allo-HSCT n=6
Imatinib n=27
20
0
0
20
40
60
Months
80
100
120
Jiang Q, et al. Blood. 2011. 17;117:3032-40.
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.
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.
TKIs versus transplant for previously TKIuntreated BP CML patients by therapy
OS
OS
PFS
EFS
EFS
Allo-HSCT was significantly superior
to TKIs.
Data from Peking University People's Hospital
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
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.
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.
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.