DASISION study: results from the 18-month follow up comparing Dasatinib to Imatinib in first-line treatment of adults with Ph+ chronic phase chronic myeloid leukemia


Results from the 18-month follow up of the Phase 3 DASISION study of Dasatinib ( Sprycel ) 100 mg once daily vs Imatinib ( 400 mg daily; Glivec, Gleevec ) in the first-line treatment of adults with Philadelphia chromosome-positive ( Ph+ ) chronic phase chronic myeloid leukemia ( CP-CML ). Results at 18 months were consistent with 12 month data in which Dasatinib demonstrated higher and faster rates of complete cytogenetic response ( CCyR ) and major molecular response 1 ( MMR ) compared to Imatinib.

Safety data from DASISION demonstrated that the most frequently reported serious adverse reactions with Dasatinib included pleural effusion ( 2% ), hemorrhage ( 2% ), congestive heart failure ( 1% ) and pyrexia ( 1%). Commonly reported adverse events ( greater than or equal to 10%, of all grades ) with Dasatinib and Imatinib included superficial edema ( 10% and 36% ), pleural effusion ( 12% and 0% ), myalgia ( 22% and 38% ), nausea ( 9% and 21% ), vomiting ( 5% and 10% ), diarrhea ( 18% and 19% ), fatigue ( 8% and 11% ), headache ( 12% and 10% ) and rash ( 11% and 17% ). Overall rates of fluid retention observed in the study were 23% with Dasatinib and 43% with Imatinib.

In the DASISION study, 78% of patients treated with Dasatinib vs 70% of patients treated with Imatinib achieved confirmed CCyR ( two consecutive assessments of CCyR at least 28 days apart ) by 18 months ( p=0.0366 ). MMR at any time was 57% for patients treated with vs. 41% Dasatinib for patients treated with Imatinib ( p=0.0002 ). Transformation to accelerated or blast phase occurred in 6 patients receiving Dasatinib and 9 patients receiving Imatinib.

Pleural effusion ( all grades ) was reported in 12% of those treated with Dasatinib, and in none treated with Imatinib; Grade 3 pleural effusion was reported in less than 1% of patients receiving Dasatinib. Thrombocytopenia occurred in 19% of those treated with Dasatinib and 10% of those treated with Imatinib. Neutropenia occurred in 22% of those treated with Dasatinib and 20% of those treated with Imatinib.

DASISION ( Dasatinib versus Imatinib Study in Treatment-Naïve CP-CML Patients ) is an open-label, randomized, Phase 3 international trial. The study enrolled 519 patients; 259 patients were randomized to receive Dasatinib and 260 patients were randomized to receive Imatinib. The primary study endpoint was the rate of confirmed CCyR by 12 months. Secondary endpoints included time-to confirmed CCyR, MMR rate and time-to MMR.

Chronic myeloid leukemia is a slow-growing type of leukemia in which the body produces an uncontrolled number of abnormal white blood cells. About 24,800 people are living with the disease in the United States. It is estimated that 4,870 new cases will be diagnosed in 2010. CML occurs when pieces of two different chromosomes break off and attach to each other. The Philadelphia chromosome contains an abnormal gene called the bcr-abl gene. This gene produces the BCR-ABL protein, which causes the body to make too many abnormal white blood cells. There is no known cause for the genetic change that causes CML.

Source: 52nd Annual Meeting of the American Society of Hematology, 2010

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