Researchers from the M. D. Anderson Cancer Center have reported that Sprycel® (dasatinib) treatment of patients with chronic myeloid leukemia (CML) who have loss of a major cytogentetic response to Gleevec® (imatinib) results in better outcomes than waiting for loss of complete hematalogic remission to institute therapy with Sprycel. The details of this study were published early online on April 28, 2009 in Cancer.[1]

Gleevec is the standard initial treatment of newly diagnosed CML. Gleevec 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. 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. Both Sprycel and nilotinib (Tasigna®) are approved by the U.S. Food and Drug administration for treatment of patients with CML who fail Gleevec. One of the issues is the timing of intervention with Sprycel or Tasigna after failure of Gleevec for treatment of chronic phase CML.

The current study evaluated data from clinical trials where Sprycel was administered after failure of Gleevec for chronic phase CML. Patients with chronic phase CML who were treated with Sprycel after loss of a major cytogenetic response following Gleevec treatment achieved a complete cytogenetic response. Patients who were treated after loss of both a major cytogenetic response and complete hematologic response had a 42% incidence of complete cytogenetic response. The two-year event-free survival was 89% for patients treated after loss of a major cytogenetic response compared with 29% for patients treated later in the disease course. These authors also reported that Sprycel was effective in patients who did not achieve a major cytogenetic response. In this group, 26% achieved a complete cytogenetic response and the two-year event-free survival was 64%.

Comments: These data suggest that Sprycel should be instituted as soon as a loss of response following Gleevec is detected. These data also suggest that patients who fail to have an initial major cytogenetic response to Gleevec should be treated with Sprycel.

Reference: