Dasatinib added to guideline for CML

November 20, 2006

Dasatinib (Sprycel, Bristol-Myers Squibb) is a new tyrosine kinase inhibitor for chronic myelogenous leukemia (CML). The Food & Drug Administration approved the drug in June, and now the National Comprehensive Cancer Network (NCCN) has added dasatinib to its CML guidelines.

Dasatinib (Sprycel, Bristol-Myers Squibb) is a new tyrosine kinase inhibitor for chronic myelogenous leukemia (CML). The Food & Drug Administration approved the drug in June, and now the National Comprehensive Cancer Network (NCCN) has added dasatinib to its CML guidelines.

Dasatinib is indicated for treatment of CML in patients for whom imatinib (Gleevec, Novartis) is ineffective or intolerable. In this population, dasatinib has produced complete cytogenetic response in 33% of patients by the six-month point during clinical studies. "So, we know dasatinib works when imatinib fails," said Susan O'Brien, M.D., professor of medicine in the leukemia department at the University of Texas M. D. Anderson Cancer Center and chair of the CML guidelines panel for NCCN. Although not all patients respond to dasatinib, a significant number do, so NCCN has concluded that dasatinib is now the go-to agent for patients not tolerating or responding to imatinib.

Although imatinib is effective in most CML patients, not all respond adequately. "At any given time-point, there may be 20% to 30% of patients qualifying for a switch to dasatinib," said O'Brien. To have two new, effective, and tolerable drugs for CML when five years ago there was little hope is "really revolutionary," she said. "Not only are response rates better, but the difference in tolerability [compared with interferon] is like night and day."

Imatinib and dasatinib are oral tablets, so they are easier to administer, and they are both much better tolerated and more effective than interferon. For these reasons, interferon has been removed from most sections of the NCCN CML guidelines.

While imatinib and dasatinib now appear to reign supreme in CML chemotherapy, resistance could potentially topple them from their thrones. According to O'Brien, resistance was a big concern when imatinib was first approved. That is the risk associated with targeted therapies, she explained. "When you target a particular protein, you get an effective treatment with few side effects." However, if a mutation occurs that changes the targeted protein, then complete resistance can occur.

Resistance has occurred with imatinib, but with less frequency than had been feared. "If anything, it's going down," said O'Brien. This may be because if the cancerous cells are eradicated by imatinib, no mutation can occur. It's too soon to celebrate, she warned. With longer-term follow-up, resistance rates could rise.

In the updated guidelines, NCCN maintained that hematopoietic stem cell transplantation (HSCT) is the treatment of choice for patients with CML as long as they are good candidates for such treatment. "HSCT has definite survival benefits, whereas, despite very promising early responses, the survival benefit, long-term toxicities, and durability of response of imatinib are unknown," NCCN stated in its guidelines.

NCCN did hint that HSCT may lose its treatment-of-choice status as evidence in favor of imatinib accumulates.

"Each year with updates we have more data," O'Brien said. As more results come in, NCCN will continue to update its CML guidelines.

Summary of changes to NCCN guidelines for CML

THE AUTHOR is a clinical writer based in the Seattle area.