Indrák K.1, Faber E.1, Demečková E.2, Demitrovičová L.3, Voglová J.4, Jindra P. 5, Markuljak I.6, Chudej J.7, Cmunt E.8, Tóthová E.9, ŠtecováN.10, Palášthy S.11, Mužík J.12, Dušek L.12

CAMELIA REGISTRY Slovakia and Czech Republic

1. Dept. Hematooncology Olomouc, CR2. Dept. Hematology and Blood Transfusion, Bratislava, SR3. Dept . Internal Medicine, Division Hematol. and Blood Transfusion, NCI, Bratislava, SR4. 4th Dept. Internal Medicine - Hematology, Hradec Králové, CR5. Dept. Hematooncology, Plzeň, CR6. Dept. Hematology and Blood Transfusion, Martin, SR7. Dept. Hematology, Banská Bystrica, SR8. Dept. Internal Medicine, General University Hospital, Prague, CR9. Dept. Hematology and Hematooncology, Košice, SR10. HEMKO Ltd., Hematology and Onco-Hematology Outpatient Dept., Košice, SR11. J. A. Rieman Health Centre, Dept. Hematology, Prešov, SR12. Institute of Biostatistics and Analyses, Brno, CR

Institute of Biostatistics and AnalysesMasaryk University

Characteristics of CML patients CAMELIA CZ and SK registry in period 2000 - 2012

4 3 2 1 7 6 13 9 1227

5439

58 67 7386

67 75 79 71

99

69 73

202 9 11

19 20 12 1218

10

1520

1920 6

6

67

114

5

414

0

20

40

60

80

100

120

<=19

9019

9119

9219

9319

9419

9519

9619

9719

9819

9920

0020

0120

0220

0320

0420

0520

0620

0720

0820

0920

1020

1120

12

Num

ber o

f pat

ient

s

Year of CML diagnosis

Total N = 1264 patients

TKI treatment (any time)

no TKI treatment Total

N = 994 N = 270 N = 1264Chronic phase 922 (92.8%) 236 (87.4%) 1158 (91.6%)Accelerated phase 51 (5.1%) 24 (8.9%) 75 (5.9%)Blast crisis 21 (2.1%) 10 (3.7%) 31 (2.5%)

TKI treatment (any time)N = 994

no TKI treatmentN = 270

prospectiveretrospective

Patients registered in CAMELIA database

in period 2000 – 2012N = 646 (TKI 518)

11

22

33

44

CAMELIA Registry

INFINITY Registry5 million inhabitants

Population distribution of the CML patients followed in the Czech CAMELIA Registry

1. Olomouc N = 211(TKI 189)

2. Hradec Králové N = 203(TKI 160)

3. Plzeň N = 186(TKI 137)

4. VFN Praha N = 46(TKI 32)

population coverage:5.6 million inhabitants5.6 million inhabitants

Patients registered in CAMELIA database in

period 2000 – 2012N = 626 (TKI 476)

5.4 million inhabitants5.4 million inhabitants

5544

11

33

CAMELIA Registry

The population distribution of the CML patients followed in the

Slovak CAMELIA Registry

1. Bratislava Hematol. N = 256(TKI 178)

2. NCI Bratislava N = 94(TKI 93)

3. Martin N = 87(TKI 59)

4. Bánská Bystrica N = 78(TKI 49)

5. HEMKO Ltd. Košice N = 66(TKI 66)

6. Košice N = 37(TKI 31)

7. Prešov * N = 8

22

•data collection in process

77

66

Male Female Total

N = 545 N = 449 N = 994Mean 51 y 52 y 51 y

Median 53 y 53 y 53 y

Min - max 17 - 86 y 17 - 89 y 17 - 89 y45%

55%

SexAge at diagnosis

0

5

10

15

20

<20

20-24

25-29

30-34

35-39

40-44

45-49

50-54

55-59

60-64

65-69

70-74

75-79

80-84 85

+

%

Age (years)

Male (N = 545)

Female (N = 449)

Characteristic of CML patients treated with TKI and enroled in CAMELIA CZ and CAMELIA SK registry in period 2000 - 2012

Total N = 994 patients

Start of TKI treatment of 994 CML patients in time - INCIDENCE

TKI in total

Imatinib 2nd line

Imatinib 1st line

DasatinibNilotinib

0

20

40

60

80

100

120

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

Num

ber o

f pat

ient

s

Year of start of treatment

TKI treatment of 994 CML patients in time - PREVALENCE

TKI in total

Imatinib 2nd line

Imatinib 1st line

DasatinibNilotinib

0

100

200

300

400

500

600

700

800

900

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

Num

ber o

f pat

ient

s

Year of treatment

0 12 24 36 48 60 72 84 96 108 120 1320.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0Pr

opor

tion

of p

atie

nts

on tr

eatm

ent

Time from start of TKI treatment (months)

Time on TKI treatment of 994 CML patients in period 2000 - 2012

TKI in total (N = 994)

TKI in 1st line (N = 710)

TKI in 2nd line (N = 284)

Log-rank test p = 0.019

0 12 24 36 48 60 72 84 96 108 120 1320.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0Pr

opor

tion

of s

urvi

ving

pat

ient

s

Time from start of TKI treatment (months)

OS of 994 CML patients on TKI treatment in period 2000 – 2012

TKI in total (N = 994)

TKI in 1st line (N = 710)

TKI in 2nd line (N = 284)

Log-rank test p < 0.001

0 12 24 36 48 60 72 84 96 108 120 1320.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

0 12 24 36 48 60 72 84 96 108 120 1320.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

0 12 24 36 48 60 72 84 96 108 120 1320.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

PFS of CP CML patients on TKI treatment in 1st line according to risk scores

low risk (N = 252)intermediate risk (N = 238)high risk (N = 152)

Sokal score

Time from start of TKI treatment (months)

Pro

porti

on o

f pat

ient

s w

ithou

t pro

gres

sion

0.088

0.022<0.001

Log-rank test plow risk (N = 269)intermediate risk (N = 293)high risk (N = 80)

Hasford score

Time from start of TKI treatment (months)

0.038

0.001<0.001

Log-rank test p

low risk (N = 550)high risk (N = 92)

EUTOS score

Time from start of TKI treatment (months)

0.160Log-rank test p

Pro

porti

on o

f pat

ient

s w

ithou

t pro

gres

sion

Pro

porti

on o

f pat

ient

s w

ithou

t pro

gres

sion

0 12 24 36 48 60 72 84 96 108 120 1320.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

0 12 24 36 48 60 72 84 96 108 120 1320.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

0 12 24 36 48 60 72 84 96 108 120 1320.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

low risk (N = 252)intermediate risk (N = 238)high risk (N = 152)

Sokal score

Time from start of TKI treatment (months)

Pro

porti

on o

f sur

vivi

ng p

atie

nts

0.070

0.2950.007

Log-rank test plow risk (N = 269)intermediate risk (N = 293)high risk (N = 80)

Hasford score

Time from start of TKI treatment (months)

Pro

porti

on o

f sur

vivi

ng p

atie

nts

0.001

0.090<0.001

Log-rank test p

low risk (N = 550)high risk (N = 92)

EUTOS score

Time from start of TKI treatment (months)

Pro

porti

on o

f sur

vivi

ng p

atie

nts

0.373Log-rank test p

OS of CP CML patients on TKI treatment in 1st line according to risk scores

1. FABER E., INDRÁK K. ET AL. Chronická myeloidní leukemie. Galén 2010

2. E. FABER, D. FRIEDECKÝ, K. MIČOVÁ ET AL. Imatinib dose escalation in two patients with chronic myeloid leukemia, with low trough imatinib plasma levels measured at various intervals from the beginning of therapy and with suboptimal treatment response, leads to the achievement of higher plas. IJH, 2010, 91(5): 897-902.

3. P. ROHOŇ, Š. ROŽMANOVÁ, J. ZAPLETALOVÁ ET AL. Výsledky liečby pacientov v chronickém fáze chronickej myelocytovej leukémie na HOK v Olomouci v rokoch 2000-2009: prognostický význam Sokalovho indexu a ELN kritérií. Transfuze a hematologie dnes, 2010, 16(4): 202-209.

4. P. ROHON, M. DIVOKA, L. CALABKOVA et al. Identification of e6a2 bcr-abl fusion in Philadephia –positive CML with marked basofilia: implication for treatment strategy. Biomed Pap 2011,155: 187-90.

5. E. FABER, J. MUŽÍK, V. KOZA ET AL. Treatment of consecutive patients with chronic myeloid leukemia in the cooperating centres form the Czech Republic and the whole of Slovakia after 2000 – a report from the population-based CAMELIA Registry. EJH 2011, 87(2):157-168.

6. VOGLOVÁ J, MUŽÍK J, FABER E, ET AL. Incidence of second malignancies during treatment of chronic myeloid leukemia with tyrosine kinase inhibitors in the Czech Republic and Slovakia. Neoplasma. 2011; 58 (3): 256-262.

CAMELIA publications 2010-2011

1. E. Faber, D. Friedecky, K. Micova, et al.: Imatinib trough plasma levels do not correlate with the response to therapy in patients with chronic myeloid leukemia in routine clinical setting.An Hematol. 01/2012; DOI:10.1007/s00277-011-1394-

2. E. Faber, A. Kuba, J. Zapletalova, et al. on Behalf of Cooperating Group: Operational Cures After Interferon-Alpha in Patients with Chronic Myeloid Leukemia in Central and Northern Moravia. JOURNAL OF INTERFERON & CYTOKINE RESEARCH, 32, 5, 2012 Ş Mary Ann Liebert,

3. Š. Rožmanová, P. Rohoň, M. Divoká, et al.: Hodnocení časné molekulární odpovědi po 3 měsících léčby imatinibem může u nemocných s chronickou myeloidní leukemií přispět k upřesnění odhadu prognózy – zkušenosti jednoho centra. Transf. Hematol. dnes 18, 2012, 66-71

4. E. Faber, D. Friedecky, K. Micova, et al.: Imatinib dose escalation in two patients with chronic myeloid leukemia, with low trough imatinib plasma levels measured at various intervals from the beginning of therapy and with suboptimal treatment response, leads to the achievement of higher plasma levels and major molecular response. IJH 04/2012; 91(5):897-902.

5. E. Faber, A. Kuba, J. Zapletalova, et al.: Interferon-alpha in chronic myeloid leukemia revisited: A long-term retrospective study in Central and Northern Moravia. Biomed Pap 2012;

CAMELIA publications 2012-2013

1. H. Klamova, E. Faber, D. Zackova et al.: Dasatinib in imatinib-resistant or intolerant CML patients: data from the clinical practise of 6 hematological centers in the Czech Republic. Neoplasma 57 (4) 355 – 359, 2010

2. A. Kreutzman, P. Rohon, E. Faber, K. Indrak et al.: Chronic myeloid leukemia patients in prolonged remission following interferon-α monotherapy have distinct cytokine and oligoclonal lymphocyte profile. PLoS ONE 01/2011; 6(8):e23022. DOI:10.1371/journal.pone.0023022

3. H. Klamová1, K. Machová Poláková1, J. Mužík2, et al.: Evaluation of 5-year imatinib treatment of 458 patients with CP-CML in routine clinical practice and prognostic impact of different BCR-ABL cutoff levels. Cancer Medicine 2, 2, 216-225, 4, 2013

4. T. Pavlik, E. Janousova, J. Mayer, K. Indrak, et al: Current survival measures reliably reflect modern sequential treatment in CML: correlation with prognostic stratifications. AJH. 2013 doi: 10.1002/ajh.23508, 6/2013

CAMELIA joint publications 2010 - 2013

1. EUTOS for CML out-study patients – accepted 240 patients

2. EUTOS for CML population-based registry – reported in total 312 patients from region of 11 mil population diagnosed in between 7/2009 - 12/2012, it means incidence of 0.81/100,000 per year

3. EURO-SKI – individual participation of the Czech republic CAMELIA centre (Olomouc, Hradec Kralove and Pilzen) through Infinity Registry

4. Pregnancy study – interest in participation of CAMELIA SR (Responsible Z. Sninska, MD, PhD.) and CR (Responsible K. Steinerova, MD, PhD.)

The proposed CAMELIA projects:

5. The prognostic significance of anemia for CML (Prof. E. Faber, MD, PhD.)

6. The validation of prognostic risk score in CML patients in real clinical practice (Z. Sninska, MD, PhD.)

7. The impact of cytogenetic abnormalities on treatment results of CML patients (Prof. M. Jarosova, MA, PhD., T. Pavlik, MA, PhD.)

8. The analyses of nilotinib treatment in clinical practice (Prof. E. Tóthová, MD, PhD.)

CAMELIA participation on ELN WP4 clinical projects and the proposed projects

Camelia group participants

Brno 4/2009

Thank you for your attention!

Olomouc 4.5.2011