AMSTERDAM, Netherlands, June 17 /PRNewswire/ --
- Data Presented at the 11th Congress of European Hematology, Organised by the European Hematology Association
Bristol-Myers Squibb presented results from four single-arm, open-label Phase II studies of dasatinib - an oral, investigational compound. The studies evaluated the efficacy and safety of dasatinib in patients in all chronic myeloid leukaemia (CML) phases (chronic, accelerated, and blast), and patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) no longer responding to or unable to tolerate current therapies, including imatinib. The data were presented at the 11th European Hematology Association (EHA) Congress.
Collectively, 789 patients were enrolled in the four studies (START-C, START-A, START-B and START-L). Patients were treated with dasatinib 70 mg twice daily; efficacy was assessed on the basis of their haematologic and cytogenetic responses and safety was assessed continuously. These studies suggest that dasatinib may be able to induce haematologic and cytogenetic responses in many patients with CML and Ph+ ALL with resistance or intolerance to imatinib. Haematologic responses are used to measure how effectively the therapy returns blood counts to normal. Cytogenetic responses are based on the number of Ph+ leukemic cells that are still present in the bone marrow.
START-C - Chronic Phase
START-C (abstract 0467) enrolled and treated 387 patients with chronic phase CML resistant or intolerant to imatinib. Major cytogenetic response, the primary objective, was achieved in 51% (197/387) of patients. Complete haematologic response was achieved in 90% (348/387) of patients. Grade 3 and 4 thrombocytopaenia and neutropaenia were reported in 47% and 47% of patients, respectively. Important non-haematologic adverse events (occurring in more than or equal to 10% of patients) included elevated liver enzymes (54%), diarrhoea (32%), headache (30%), rash (22%), superficial edema (20%), and pleural effusion (17%).
START-A - Accelerated Phase
The START-A (abstract 0159) enrolled 192 patients with accelerated phase CML resistant or intolerant to imatinib; 174 patients received treatment. Major haematologic response, the primary objective, was achieved in 59% (102/174) of patients. Major cytogenetic response was achieved in 34% (60/174) of patients. Grade 3 and 4 thrombocytopaenia and neutropaenia were reported in 82% and 73% of patients, respectively. Important non-haematologic adverse events included diarrhoea (61%), rash (27%), pleural effusion (25%), superficial edema (20%), and GI haemorrhage (12%).
START-B - Myeloid Blast Crisis
The START-B (abstract 0150) enrolled and treated 109 patients with myeloid blast crisis resistant or intolerant to imatinib. Major haematologic response, the primary objective, was achieved in 49% (53/109) of patients. Major cytogenetic response was achieved in 44% (48/109) of patients. Grade 3 and 4 thrombocytopaenia and neutropaenia were both reported in 64% and 64% of patients, respectively. Important non-haematologic adverse events included diarrhoea (37%), pleural effusion (30%), vomiting (20%), nausea (18%), peripheral edema (17%), rash (11%) and asthenia (11%).
START-L - Lymphoid Blast Crisis or Ph+ ALL
The START-L (abstract 0653) enrolled 101 patients; of those, 94 patients with CML in lymphoid blast crisis (48) or Ph+ ALL (46) resistant or intolerant to imatinib received treatment. Major haematologic response, the primary objective, was achieved in 33% (16/48) of patients in lymphoid blast crisis, and 39% (18/46) of patients with Ph+ ALL. Major cytogenetic response was achieved in 44% (21/48) of patients in lymphoid blast crisis, and 46% (21/46) of patients with Ph+ ALL. Grade 3 and 4 thrombocytopaenia were reported in 88% of lymphoid blast crisis and 78% of Ph+ ALL patients. Grade 3 and 4 neutropaenia were reported in 81% lymphoid blast crisis and 74% of Ph+ ALL patients. Important non-haematologic adverse events included diarrhoea (30%), nausea (22%), vomiting (17%), pleural effusion (16%), headache (15%), rash (15%), peripheral edema (13%), and gastrointestinal hemorrhage (2%).
About Dasatinib
Dasatinib was filed in the European Union in January 2006 and was granted positive opinions on the orphan drug status for Ph+ ALL and CML treatments, but has not yet been granted final designations. Dasatinib was granted orphan product designation for CML and Ph+ ALL by the U.S. FDA in November 2005. Orphan product designation has been applied for in several other countries.
About CML and Ph+ ALL
CML is a cancer of the blood and bone marrow that usually occurs during or after middle age and rarely occurs in children. The worldwide incidence of CML is relatively uniform and represents about 15% of all leukaemias. The incidence of resistance increases with the number of years on treatment and severity of disease.
Ph+ ALL is a rapidly progressive cancer of the blood and bone marrow that usually occurs in adults. Patients with advanced Ph+ ALL generally develop resistance more rapidly than CML patients, including those in blast phase (an average of 2 months versus 10 months, respectively).
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global pharmaceutical and related health care products company whose mission is to extend and enhance human life.
