The initial report of a Phase II study evaluating Sprycel® (dasatinib) combined with chemotherapy for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) indicates that 94% of patients achieve a complete remission. These findings were recently published in the journal Blood.
Adult ALL is a malignant disease or cancer of the blood characterized by the rapid uncontrolled growth of abnormal, immature white blood cells known as lymphoblasts. There are approximately 5,000 new cases of adult ALL each year in the United States, with approximately 1,500 deaths. Up to 40% of adults with ALL have Ph+ ALL. Adults with Ph+ ALL usually receive Gleevec® (imatinib) in the induction regimen.
Sprycel is a tyrosine kinase inhibitor that may be used for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy. Previous studies have suggested that Sprycel is also effective for first-line therapy of Ph+ ALL. Researchers from Italy reported that Sprycel monotherapy resulted in a 100% complete hematologic remission rate in 36 patients with newly diagnosed Ph+ ALL. Researchers affiliated with the European Working Group on Adult ALL (EWALL) reported a 100% complete hematologic remission rate for 22 patients with newly diagnosed Ph+ ALL treated with Sprycel plus chemotherapy. Studies have been ongoing to determine the optimal incorporation of Sprycel into a tolerable regimen for induction, consolidation, and maintenance therapies.
In the current Phase II study, researchers from M. D. Anderson Cancer Center evaluated 35 newly diagnosed adult patients with Ph+ ALL. Patients initially underwent treatment with a combination of Sprycel, hyperCVAD, and high-dose cytarabine and methotrexate. Once patients achieved a complete remission, maintenance therapy consisted of daily Sprycel indefinitely with monthly vincristine and prednisone for two years. The researchers reported that 33 of the 35 patients (94%) achieved a complete remission with two patients being lost before assessment due to infection. This is an initial report of an ongoing study, and at a median follow up of 14 months survival endpoints have not yet been reached. However, the estimated two-year survival is 64%. So far, grade 3 and 4 side effects include bleeding, fluid build-up in the lungs (pleural effusion), and fluid around the heart (pericardial effusion).
These researchers concluded that the combination of Sprycel and chemotherapy is “effective in achieving long term remissions in patients with newly diagnosed Ph+ ALL.” The overall and disease-free survival data will provide additional efficacy data for this promising combination for newly diagnosed Ph+ ALL patients.
 Ravandi F, O’Brien S, Thomas D, et al. First report of phase II study of dasatinib with hyperCVAD for the frontline treatment of patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia. Blood. [Early online publication May 13, 2010].
 Foa R, Vitale A, Guarini A, et al. Dasatinib monotherapy effective and feasible as first-line treatment of adult Philadelphia-chromosome positive acute lymphoblastic leukemia: Final results of the GIMEMA LAL1205 study. Blood. 2008;112:119, abstract number 305
 Cayuela J-M, Recher C, Leguay T, et al. Dasatinib (Sprycel®) and chemotherapy for first-line treatment of elderly patients with de Novo Philadelphia Positive ALL: Results of the first 22 patients included in the EWALL-PH-01 Trial (on behalf of the European Working Group on Adult ALL (EWALL). Blood. 2008;112:1004, abstract 2920.