Dasatinib Drug Use Results Surveys For All Cases As Nationwide Real World Data

Dasatinib is a BCR-ABL kinase inhibitor that was approved in Japan in January 2009 for the treatment of chronic myeloid leukemia (CML) and Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). This study was aimed to acquire the background information on the patients treated with dasatinib and early data related to safety and efficacy, which would provide important information to ensure the appropriate use of dasatinib.

We conducted the nation-wide surveillance for all the patients who used dasatinib for 3 years after starting this medicine. The target number of patients was 800. The principal aims of the survey were to identify: (1) unknown adverse drug reactions, (2) the circumstances under which adverse drug reactions occur in real-world use of the drug, and (3) the factors that may affect safety and efficacy. Especially, we focused on the circumstances of development and incidences of bone marrow depression/cytopenia, hemorrhage, fluid retention, cardiovascular events and abnormal electrocardiogram (QT prolongation), hepatobiliary disorders, and interstitial lung diseases.

This survey included 903 evaluable subjects for whom survey sheets have been returned to date, June 27, 2012. The composition of the registered cases was: chronic-phase CML 375, accelerated-phase CML 80, blastic-phase CML 133, Ph+ ALL 312, and others 3. Median age was 62 years (range, 7-92) in the chronic-phase CML group, 63.5 years (range, 9-84) in the accelerated-phase group, 63 years (range, 18-86) in the blastic-phase CML group, and 60 years (range, 5-92) in the Ph+ ALL group. 879 patients were previously treated with imatinib. The proportion of imatinib resistant to imatinib intolerant (resistant/ intolerant) in chronic-phase CML was 57.6%/42.4%, in accelerated-phase CML was 84.0%/16.0%, in blastic-phase CML was 78.4%/21.6%, and in Ph+ ALL was 65.1%/34.9%. The median treatment duration (days) was 414 in the chronic-phase CML group, 303.5 in the accelerated-phase CML group, 81 in the blastic-phase CML group, and 96.5 in the Ph+ ALL group. The frequent adverse drug reactions (10% or more) were thrombocytopenia 45.7%, anemia 36.7%, leucopenia 30.7%, pleural effusion 28.0%, and neutropenia 23.8% (all grades). The incidence of bone marrow depression/cytopenia was 56.1%, hemorrhage 10.7%, fluid retention 37.1%, cardiovascular events and abnormal electrocardiogram 4.5%, hepatobiliary disorders 20.4%, and interstitial lung diseases 3.5%. The incidences of bone marrow depression/cytopenia, hemorrhage, and fluid retention in chronic-phase CML were 49.6%, 5.9%, and 28.8%, respectively, and tended to be lower than in the other phases (accelerated phase and blastic phase CML and Ph+ ALL). Additionally, we will report the intervals before the onset of adverse drug reactions, the circumstances of continuation of administration, and factors that appear to affect safety or efficacy based on the latest data update.

The information in this all-case drug use results survey will be useful to ensure the appropriate use of dasatinib in real-world patients.

Kurokawa:Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Consultancy, Research Funding. Nishizawa:Bristol-Myers K.K.: Employment. Tetsuka:Bristol-Myers K.K.: Employment. Meiji:Bristol-Myers K.K.: Employment. Hiroshi:Bristol-Myers K.K.: Employment.