Sprycel for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant to or intolerant of imatinib mesylate

Purpose: On June 28, 2006, the U.S. Food and Drug Administration approved dasatinib (Sprycel; Bristol-Myers Squibb), a new small-molecule inhibitor of multiple tyrosine kinases, for the treatment of adults with chronic phase, accelerated phase, or myeloid or lymphoid blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy including imatinib. This summary reviews the database supporting this approval. Experimental Design: Four single-arm multicenter studies supported the efficacy and safety of dasatinib. The primary efficacy end point in chronic phase CIVIL was major cytogenetic response. The primary end point in accelerated phase, myeloid phase, and lymphoid blast phase CML, and Ph+ ALL was major hematologic response. Results: The four studies combined enrolled 445 patients. In patients with chronic phase CIVIL, the major cytogenetic response rate was 45% with a complete cytogenetic response rate of 33%. Major hematologic response rates in patients with accelerated phase CIVIL, myeloid CIVIL, lymphoid blast CIVIL, and Ph+ ALL were 59%, 32%, 31%, and 42%, respectively. Median response durations in chronic phase, accelerated phase, and myeloid phase CIVIL had not been reached. The median durations of major hematologic response were 3.7 months in lymphoid blast CIVIL and 4.8 months in Ph+ ALL. Common toxicities with dasatinib included myelosuppression, bleeding, and fluid retention. Conclusions: This report describes the Food and Drug Administration review supporting the approval of dasatinib for CIVIL and Ph+ ALL based on the rates and durability of cytogenetic and hematologic responses.