Imatinib Resistance and/or Intolerance in Clinical Practice in Europe: The “Unmet Needs in CML and Ph+ALL” (UNIC) Study.

Imatinib is widely used for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL), and is associated with improved response rates in these patients. However, the management of patients who show resistance or intolerance to imatinib has been identified as an unmet need. The UNIC study aimed to quantify this unmet need. UNIC is a cross-sectional study, with retrospective chart review of patients currently treated for CML or Ph+ALL in Austria, Belgium, France, Italy, Netherlands, Spain, Sweden and UK. Patients were recruited September 2006-March 2007. The study was designed to estimate the proportion of

• patients ever treated with imatinib and

• imatinib-treated patients who have experienced imatinib resistance and/or intolerance (primary objectives).

A registry was collected of potentially-eligible patients - those aged ≥18 years and treated for CML/Ph+ALL at the participating centers (academic, non-academic, private clinic or other). Case Report Forms (CRFs) were completed for patients who met the inclusion criteria, until the recruitment target was reached. Data were collected at the most recent visit and retrospectively through clinical chart review. Of the 4139 patients in the registry, CRFs were completed for 1716 and analyzable for 1599 (CML, n=1551; Ph+ALL, n=48). Characteristics of the included population were representative of those of the registry. Of the included CML patients, 98% were in chronic phase and 2% were in advanced phases. In total, 1493 (96%) CML and 46 (96%) Ph+ALL patients had received imatinib. By the last observation, 48% of all imatinib-treated patients needed a change in imatinib dose, and >20% discontinued imatinib therapy (CML, 21%; Ph+ALL, 37%). A patient was defined as imatinib resistant if reported as such by the physician in the medical chart, and intolerant to imatinib (or other concurrent treatment) if toxicity led to a change in imatinib use, as reported in the medical chart. Imatinib resistance and treatment intolerance reported during the study are shown in the table. Seven percent of CML and Ph+ALL patients discontinued imatinib due to toxicity.

This is the largest European observational study of CML/Ph+ALL patients to date. As expected, nearly all patients were exposed to imatinib therapy. Nearly half of all imatinib-treated CML and Ph+ALL patients experienced resistance to imatinib and/or intolerance to treatment including imatinib.