CML Registry

Joerg Hasford, MDLudwig-Maximilians UniversityMunich, Germany

Speaker disclosed relations to Novartis

European CMLEuropean CML Registry Registry

M. Baccarani Italy

J. Guilhot France

B. Simonsson Sweden

Joerg Hasford Germany

IBE Department of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität München

Email: has@ibe.med.uni-muenchen.de

StructureStructure

Objectives Clinical Data Epidemiological data Treatment survey Discussion Conclusions

European CML RegistryEuropean CML RegistryOBJECTIVESOBJECTIVES

Clinical to develop and validate

a comprehensive prognostic model which allows to optimise individual treatment choices

in particular a prognostic model for treatment with imatinib

to evaluate the impact of therapeutic drug monitoring, pharmacokinetics

and patients’ compliance during the course of CML

the sequelae of discontinuation of treatment after complete cytogenetic remission (CCR)

the mechanisms and sequelae of imatinib failure

European CML RegistryEuropean CML RegistryOBJECTIVESOBJECTIVES

Epidemiological to collect baseline and treatment data of representative

samples of CML patients of all European countries to estimate the incidence of CML stratified for age, sex and

region to evaluate the medical management of CML patients using

the ELN recommendations (Blood 2006;108:1809-20)

European CML RegistryEuropean CML RegistryOBJECTIVESOBJECTIVES

General to promote quality controlled molecular monitoring to foster continued medical education and spread of

excellence to develop and keep updated a core data set for CML to provide a platform for the expedited evaluation of new

treatments to promote European trials, meta-analyses and pooled data

analyses

Data provided by the Data provided by the cooperating study groupscooperating study groups

Study Type Treatment optionsn

I - ICSG CML 21 Phase II imatinib 800 mg 82

I - ICSG CML 22 Phase III imatinib 400 mg vs 800 mg 117

I - ICSG CML 23 Phase II imatinib 400mg365

German gr. CML IV Phase II 4 arms imatinib treatment904

E - CML/PETHEMA Phase III imatinib treatment200

E - RELMC Registry any imatinib therapy 318

Nordic CML001 Phase III imatinib 400mg vs 800mg103

Nordic CML002 Phase II imatinib 400 mg vs 400mg+PEG-IFN50

ROM – Registry Registry any imatinib therapy 33

F - Spirit Phase III 4 arms imatinib treatment370

PL - Registry Registry any imatinib therapy267

Total2809

Inclusion criteriaaccording to the CML Guidelines (Baccarani et al. Blood 2006)

Patients with Philadelphia positive or BCR/ABL positive CML in early chronic phase* treated with a tyrosine kinase inhibitor (mainly imatinib)

No age limitations

2062** of 2809 patients were included in the registry

* Early chronic phase: patients in chronic phase and therapy begin with tyrosine kinase inhibitors within six months after diagnosis.

** the number of accepted patients may decrease or increase slightly as baseline and follow up data are not available for all patients yet; therefore inclusion criteria are sometimes still missing.

Study data expected for the Study data expected for the European CML-RegistryEuropean CML-Registry

Cooperation with the Austrian study group, the OSHO study group, a Russian study group, and the CAMELIA / INFINITY are in progress.

country n Median age in years n Sex (% female)

France 370 52 (18-81) 370 39

German group 565 53 (16-83) 565 41

Italy 563 52 (18-84) 559 40

Nordic group 136 51 (17-82) 91 45

Poland 86 48 (18-72) 89 42

Romania 7 38 (27-57) 10 40

E-PETHEMA 197 44 (18-71) 197 45

E-RELMC 131 46 (19-87) 131 35

European CML-Registry:European CML-Registry:Baseline characteristicsBaseline characteristics

European CML-Registry: European CML-Registry: ResultsResults

Cytogenetic remission at month 12

complete partial minor minimal no response

Registry* (n=802) 75.4 % 13.0 % 3.6 % 3.9 % 4.1 %

Female* (n=325) 76.6 % 10.8 % 3.1 % 4.6 % 4.9 %

Male* (n=477) 74.6 % 14.5 % 3.9 % 3.4 % 3.6 %

IRIS 69.0 % 16.0 %

All patients treated with imatinib 400 mg with or without co-medication, and data included if t > 2 months.

* data was available of the German, Italian and Nordic study group

CML-Incidence and treatment survey

Population: Bavaria ~12.4 million inhabitants

Data base: The Bavarian Association of SHI-Accredited Physicians (KVB)

Coverage: 83.5% of outpatient care in Bavaria (10.4 million)

Time: 2003 - 2005

CML case definition: ICD C92.1 Chronic myeloid leukemia and treatment with either imatinib, interferon alpha, hydroxyurea or busulfan,treatment > 1 year

Joerg Hasford, Martin Tauscher

Results - Incidence

2004 201 new CML-patients → 1.93 / 100,000 / year

2005 187 new CML-patients → 1.80 / 100,000 / year Age (median)

Male: 50.7 % 63 years

Female: 49.3 % 65 years

Population (SHI): 10,387,207

Incidence of CML - International Data (WSP)

Bavaria UK 1 UK 2

Women 1.06 0.47 0.67

Men 1.36 0.72 1.00

All persons 0.83

1 Mc Nally RJQ et al. Hematol Oncol 1997;15:173-189.2 Phekoo KJ et al. Hematologica 2006;91:1400-1404.

Incidence per 100’000

ConclusionsConclusions

• The European CML Registry has been successfully established.

• The cytogenetic remission rates 12 months after treatment initiation with imatinib 400 mg/d have been successfully reproduced.

• First epidemiological analyses indicate incidence estimates similar to the US, but comparatively high for Europe.

• Clinical trials select considerably younger and preferably male patients with a more benign prognosis.

• First results of the treatment survey indicate room for improvement.

Thank you very much for your cooperation!

Denmark / Finland / Israel /Norway / Sweden: Prof. B. Simonsson (Uppsala)

France: Dr. J. Guilhot (Poitiers)

Czech Republic / Germany / Switzerland:

Prof. R. Hehlmann (Mannheim)

Italy: Prof. M. Baccarani (Bologna)

Poland: Prof. A. Hellmann (Gdansk)

Romania: Prof. A. Colita (Bucharest)

Spain: Prof. F. Cervantes (Barcelona)

Spain: Prof. J.L. Steegmann (Madrid)

The Bavarian Association of SHI-Accredited Physicians (KVB) M. Tauscher

The European CML Registry Group in Munich

D. Lindörfer

M. Pfirrmann, Dipl.Stat., M.Sc., Dr. rer.biol.hum.

J. Hasford, Prof. Dr.

Joerg Hasford, MDLudwig-Maximilians UniversityMunich, Germany