Researchers from the M.D. Anderson Cancer Center have reported that Sprycel® (dasatinib) produces rapid and complete cytogenetic response in patients with newly diagnosed chronic myeloid leukemia (CML). These data were presented at the 2008 meeting of the American Society of Clinical Oncology in Chicago May 30-June 2.¹

Gleevec® (imatinib mesylate) is the standard initial treatment of newly diagnosed CML. Gleevec produces high rates of complete cytogenetic responses (70-85%) and of major molecular responses (20-40%), and has improved progression-free and overall survival. 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.

Sprycel and Tasigna® (nilotinib) are two new agents that have been developed for the treatment of patients with BCR-ABL-positive CML and acute lymphoblastic leukemia (ALL); these agents appear to have great promise for the treatment of patients who fail Gleevec. Sprycel and Tasigna are both approved by the U.S. Food and Drug Administration for treatment of patients who fail or are intolerant to Gleeevec. Other tyrosine kinases are under development and being tested in the clinic. Studies are beginning to determine if Sprycel or Tasigna may be superior to Gleevec for the initial treatment of newly diagnosed patients with CML.

Researchers reported that Sprycel produced rapid and complete cytogenetic responses in a high percentage of 40 newly diagnosed patients with CML. Patients were randomized to be treated at a dose of 100mg/day given as a single dose or 50 mg given BID. Researchers in this trial evaluated the rates of complete cytogenetic response in patients receiving Sprycel or Gleevec at a dose 400 or 800 mg/day. The following table summarizes the main findings of this trial to date.

These authors reported that at 12 months, the major molecular response rate was 32%. Sprycel was well tolerated; the main toxicity was musculo-skeletal pain. Approximately half the patients receiving Sprycel required transient interruption of treatment. These authors suggested that Sprycel produced more rapid and possibly more complete cytogenetic responses than 400 mg/day of Gleevec.

Comments: Sprycel may or may not be superior to 800 mg/ day of Gleevec, and randomized trials will be needed to sort this out.

Related News:

Sprycel® (Dasatinib) Confirmed Effective for Gleevec-Resistant Patients with Chronic Myeloid Leukemia (CML) (1/2/2008)

Sprycel® Effective for CML in Accelerated Phase after Failure of Gleevec® (5/23/2007)

Sprycel® Very Active for Treatment of CML in Blast Crisis (4/19/2007)

Sprycel® Effective after Gleevec® Failure in Patients with CML in Chronic Phase (3/14/2007)

Sprycel® Superior to High-Dose Gleevec for Gleevec-Resistant CML (1/18/2007)

Reference:

¹ Borthakur G, Kantarjian HM, O/Brien SM, et al. Efficacy of dasatinib in patients (pts) with previously untreated chronic myelogenous leukemia (CML) in early chronic phase (CML-CP). Journal of Clinical Oncology. 2008;26:abstract 7013.