In 2002, the FDA approved the drug Gleevec (imatinib) as a first-line therapy for adults with chronic myeloid leukemia (CML) caused by the fusion gene BCR-ABL, known as the Philadelphia chromosome. The approval dramatically extended the lives of patients with the condition and, in many ways, ushered in the era of molecularly-targeted treatments against cancer. Now worldwide phase II clinical trial results presented at the American Society for Clinical Oncology (ASCO) Annual Meeting 2017 show the promise of the second-generation drug Sprycel® (dasatinib), also aimed at BCR-ABL fusion in CML, in a new population, namely pediatric patients.
Gleevec is the standard initial treatment of newly diagnosed chronic myeloid leukemia (CML). Imatinib produces high rates of complete cytogenetic responses (70% to 85%) and of major molecular responses (20% to 40%) and has improved progression-free and overall survival.1 2 However, Gleevec does not eradicate the BCR-ABL clones in most patients as detected by polymerase chain reaction (PCR) monitoring. Furthermore, a small but significant fraction of patients will develop Gleevec-resistance or are intolerant to the drug. Patients who fail or are intolerant to Gleevec now have treatment alternatives other than allogeneic stem cell transplantation. Chronic myeloid leukemia makes up about 5 percent of all childhood leukemias, resulting in about 150 cases per year in the United States.
Sprycel was developed for the treatment of patients with BCR-ABL-positive CML and acute lymphoblastic leukemia (ALL) and is approved by the US Food and Drug Administration for treatment of patients who fail or are intolerant to Gleeved.
The current study evaluated 113 pediatric patients and is the largest prospective trial of pediatric patients with CML, offered at 80 medical centers in 18 countries.
Overall 75% of these patients who had previously failed or did not tolerate Gleevec saw improved progression-free survival 48 months after starting treatment with Sprycel. Of newly diagnosed pediatric patients who were previously untreated more than 90% saw progression-free survival at 48 months of beginning Sprycel treatment. In addition to the ability of Sprycel to control CML, it appeared to work very quickly. Within 3 months of beginning Sprycel treatment more than 50% of patients who had previously failed Gleevec responded to treatment.