1. CML Registry Joerg Hasford, MD Ludwig-Maximilians University Munich, Germany Speaker disclosed relations to Novartis

2. European CML Registry M. BaccaraniItaly J. GuilhotFrance B. SimonssonSweden Joerg HasfordGermany IBEDepartment of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität München Email:has@ibe.med.uni-muenchen.de

3. Structure  Objectives  Clinical Data  Epidemiological data  Treatment survey  Discussion  Conclusions

4. European CML Registry OBJECTIVES 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

5. European CML Registry OBJECTIVES 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)

6. European CML Registry OBJECTIVES 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

7. Data provided by the cooperating study groups StudyType Treatment optionsn I - ICSG CML 21Phase IIimatinib 800 mg 82 I - ICSG CML 22Phase IIIimatinib 400 mg vs 800 mg 117 I - ICSG CML 23Phase IIimatinib 400mg365 German gr. CML IVPhase II4 arms imatinib treatment904 E - CML/PETHEMAPhase IIIimatinib treatment200 E - RELMCRegistryany imatinib therapy 318 Nordic CML001Phase IIIimatinib 400mg vs 800mg103 Nordic CML002Phase IIimatinib 400 mg vs 400mg+PEG-IFN50 ROM – RegistryRegistryany imatinib therapy 33 F - SpiritPhase III4 arms imatinib treatment370 PL - RegistryRegistryany imatinib therapy267 Total2809

8. Inclusion criteria according 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.

9. Study data expected for the European CML-Registry Cooperation with the Austrian study group, the OSHO study group, a Russian study group, and the CAMELIA / INFINITY are in progress.

10. countrynMedian age in yearsn Sex (% female) France 37052 (18-81)37039 German group 56553 (16-83)56541 Italy 56352 (18-84)55940 Nordic group 13651 (17-82)9145 Poland 8648 (18-72)8942 Romania 738 (27-57)1040 E-PETHEMA 19744 (18-71)19745 E-RELMC 13146 (19-87)13135 European CML-Registry: Baseline characteristics

11. European CML-Registry: Results Cytogenetic remission at month 12 completepartialminorminimalno 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

12. 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

13. Results - Incidence 2004201 new CML-patients→1.93 / 100,000 / year 2005187 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

14. Incidence of CML - International Data (WSP) BavariaUK 1 UK 2 Women1.060.47 0.67 Men1.360.721.00 All persons0.83 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

15. Conclusions 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.

16. 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

17. The European CML Registry Group in Munich D. Lindörfer M. Pfirrmann, Dipl.Stat., M.Sc., Dr. rer.biol.hum. J. Hasford, Prof. Dr.

18. Joerg Hasford, MD Ludwig-Maximilians University Munich, Germany