CML Patients In Clinical Trials Represent Fairly Well The General Population Of CML Patients: A Comparative Analysis Of 5803 Patients From The EUTOS Registry
Authors: Hoffmann Verena S , Lindoerfer Doris , Pfirrmann Markus , Saussele Susanne , Hochhaus Andreas , Engel Jutta , Guilhot Joelle , Rosti Gianantonio , Mayer Jiri , Indrak Karel , Castagnetti Fausto , Turkina Anna , Zaritskey Andrey , Steegmann Juan Luis , Hellmann Andrzej , Thielen Noortje , Cervantes Francisco , Simonsson Bengt , Colita Adriana , Clark Richard E. , Almeida Antonio , Labar Boris , Marin David , Ossenkoppele Gert J. , Bogdanovic Andrija , Dyagil Irina , Porkka Kimmo , O'Brien Stephen , Griskevicius Laimonas , Panagiotidis Panagiotis , Thaler Josef , Zupan Irena , Lejniece Sandra , Everaus Hele , Masszi Tamás , Melanthiou Frederiki , Hehlmann Rüdiger , Hasford Joerg , Baccarani Michele 
Published: October 2019

Abstract

Introduction
The centerpiece of the European Treatment and Outcome Study (EUTOS) for Chronic Myeloid Leukemia (CML) is a registry collecting representative samples of CML patients in Europe. The In-Study section of the registry combines data of patients enrolled in investigator-sponsored prospective studies of treatment with imatinib-based regimens. The population-based (PB) section includes data of all newly diagnosed CML patients in specified regions of 27 European countries in an attempt to represent the general population of CML patients.

Aims
There is a common assumption that patients enrolled in prospective trials are highly selected, do not represent the ‘typical’ patient and that thus the results of such trials may not be easily generalized to all patients. Thus we analyzed possible differences in the baseline characteristics of the two patient groups. Available were age, sex, EUTOS score, phase of disease, spleen enlargement, platelets, leukocytes, and percentages of blasts, eosinophils, and basophils in peripheral blood.

Methods
For all analyzed factors we calculated distribution parameters or percentages depending on the scale of the factor. To identify significant differences we used χ2-tests and Mann-Whitney U-tests. Level of significance was 0.05.

Results
The In-Study section included 2346 patients from study groups in Germany, Italy, France, Spain, the Nordic study group, the Netherlands, and the United Kingdom, newly diagnosed from 2002 to 2006. The PB section of the registry included 3457 patients newly diagnosed with CML from 2008 to 2012 in 27 European countries.
The median age at diagnosis of In-Study patients (51 years (18-88)) was significantly lower than the age of the general population newly diagnosed with CML (56 years (18-99), p<0.0001). Also, while in the PB section the percentage of male patients was 54%, in the In-Study section the percentage was significantly higher (60%, p<0.0001).
The median spleen size enlargement (cm below costal margin) did not differ significantly between the two groups (In-Study (1 cm (0-38), PB section 0 cm (0-40)).
While 7% of patients in the PB section were not in chronic phase, this was only true for less than 1% of patients included into the In-Study section. Accordingly, there were significant differences (both p<0.0001) regarding percentages of blast cells in peripheral blood (In-Study: 1% (0-14), PB 1% (0-92)) and leukocytes (In-Study: 74 x109/L (20-650), PB 85 x109/L (3-932)). There were no differences in percentage of basophils, eosinophils and in platelet count.
The EUTOS risk score was developed to predict the treatment success of patients in chronic phase and thus is calculated for patients in chronic phase only. In the In-Study section 10.5% of patients had a high EUTOS risk score while the percentage in the general population was 11.4%. The resulting difference was not significant (p=0.3374).

Conclusions
With a total of 5803 patients included in the two sections of the EUTOS registry analyzed for this work, the combined data allow a unique insight into the characteristics of CML patients in Europe. The comparison between the In-Study and the PB sections shows some important differences between the two populations, such as age and sex distribution. However, several other clinical and hematological factors which are known to be predictive for treatment outcome did not differ substantially. We conclude that patients enrolled in investigator-sponsored studies represent fairly well the general population of CML patients in Europe, with the exception of sex and age distribution, which may limit the value of the calculations of overall survival because those are affected by both age and gender.

Disclosures:
Hoffmann: Novartis Oncology: Research Funding. Lindoerfer:Novartis Oncology: Research Funding. Pfirrmann:Novartis: Consultancy. Saussele:Novartis Oncology: Honoraria, Research Funding. Hochhaus:Novartis: Research Funding; Bristol Myers Squibb: Research Funding. Rosti:Novartis: Consultancy, Speakers Bureau; Bristol Myers Squibb: Consultancy, Speakers Bureau; Ariad: Consultancy, Speakers Bureau; Roche: Speakers Bureau; Pfizer: Speakers Bureau. Mayer:Roche: Consultancy, Research Funding; Glaxo: Consultancy, Research Funding. Castagnetti:Bristol-Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Turkina:Bristol Myers Suibb: Consultancy; Novartis Pharma: Consultancy. Zaritskey:University of Heidelberg: Research Funding. Steegmann:Novartis Pharma: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding. Cervantes:Bristol Myers Squibb: Speakers Bureau; Teva Pharmaceuticals: Membership on an entity’s Board of Directors or advisory committees; Pfizer: Membership on an entity’s Board of Directors or advisory committees; Novartis: Speakers Bureau. Porkka:BMS: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau. Griskevicius:Novartis: Consultancy, Research Funding. Panagiotidis:GSK: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Hehlmann:Novartis: Research Funding; Bristol Myers Squibb: Consultancy. Baccarani:Novartis: Research Funding.