CML TREATMENT: QIAN JIANG

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



from single center


single center



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.

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 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

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

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

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

Outline



from single center


single center



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

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


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

Imatinib versus nilotinib for newly diagnosed patients in chronic phase: CCR rate

28 27 27

31 31 30

P=0.003 P=0.039


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


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.


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


Outline



from single center


single center



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

•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

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.

• 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


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.


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.


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.


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.


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.


TKIs versus transplant for previously TKI-untreated BP CML patients by therapy

OS

EFSEFS

OS

PFS

Allo-HSCT was significantly superior

to TKIs.


Outline



from single center


single center



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.

Education

CML TREATMENT: QIAN JIANG