European Sub-Registry of Chronic Myelogenous Leukemia (CML) Patients (pts) in Failure after Imatinib Therapy (IFP): Rationale, Study Design and Current Enrollment.

The purpose of the registry is to collect existing cases of pts who failed imatinib therapy. Since the drug has been registered most of information on safety and efficacy were collected through clinical trials. Thus the true rate of failure is currently unknown. Members of the European LeukemiaNet agreed to establish a subregistry with the aim of collecting these cases. Failure is defined as

1. efficacy failure i.e. no hematological response (HR) or cytogenetic response (CyR), unsatisfactory response, loss of response, according to the European Guidelines criteria (Baccarani et al, Blood 2006) and

2. documented toxicity leading to discontinuation of imatinib.

Objectives are to describe the sub-categories of failure and main toxicities, demographic patterns, clinical and biological profiles of pts (at diagnosis, at the beginning of imatinib therapy, at time of failure), dose and duration of imatinib therapy until failure was recorded, therapeutic decision after failure, and survival status.

Eligibility criteria: To be included in the Registry, pts who failed imatinib therapy must be 18 years old or more with Ph+ CML in chronic phase at the onset of imatinib therapy. Pts are eligible, being included in prospective studies or not.

Data collection: based on notification, data is prospectively centralized and quality controlled. The planned period for registration is 2005–2007 and 1000 cases are expected. Final analyses will be conducted overall, by groups: imatinib first line/not first line and by categories of failures.

Results: As of July, 2006, 378 pts,(M: 56%, F 44%), were recorded. Median age at diagnosis was 51 (range 12–80). Participating countries were: Austria (4 pts), Denmark (13), Finland (18), France (236), Germany (39), Israel (34), Italy (10), Netherlands (11), Spain (13). Thirty seven percent of pts were never included in prospective studies at the time of failure. Reason for registration was no or unsatisfactory response in 30% of the cases including no complete HR (2%), not any CyR (12%), no major CyR (16%). Loss of responses occurred in 41% of the cases including hematological relapse (6%) cytogenetic relapse or progression (12%), progression to accelerated phase or blast crisis (23%). Discontinuation because of toxicity was recorded in 13% of the cases. Sixteen percent of the pts presented toxicity combined with unsatisfactory response.

Policy: The IFP sub-registry is supported by a grant from the 6^th European framework program “LifeSciHealth”. This collaborative study is linked with the European CML Registry (Work Package 4). This study is conducted in accordance with principles and guidelines of the European Community and Helsinki protocol and was approved by French authorities. In conclusion, this registry has been successfully established and already provides important information on subcategories of imatinib failure pts.