Dasatinib shows promising clinical benefit in patients with chronic myelogenous leukaemia who have failed first-line imatinib

Researchers have reported that the oral dual BCR/ABL and family tyrosine kinase inhibitor, Sprycel® (dasatinib), achieves higher response rates compared with high-dose imatinib, in a Phase II study of patients with imatinib-resistant chronic-phase (CP) chronic myelogenous leukemia (CML), in a study published in the journal Blood this week.

Imatinib, which inhibits the BCR-ABL tyrosine kinase implicated in the pathophysiology of CML, is the therapy of choice for previously untreated chronic-phase CML, achieving complete cytogenetic remission in up to 80% of patients. However, most patients treated with imatinib usually harbor minimal residual disease that eventually leads to disease recurrence.

Dasatinib, is approximately 300 times more potent against BCR-ABL than imatinib, and is currently approved for the second-line treatment of imatinib-resistant CML. In this setting, dasatinib has been shown to induce complete cytogenetic remission in 75% of imatinib-intolerant patients and 40% of imatinib-resistant patients.

In the current study, patients with CP CML resistant to imatinib were randomized to receive 140 mg dasatinib or high-dose imatinib (800 mg). At 15 months, the proportion of patients with a complete haematological response was significantly higher in patients receiving dasatanib versus imatinib (93% vs. 82%, respectively; P = .034), which included complete cytogenetic responses (40% vs. 16%, respectively; P = .004). In addition, the proportion of patients with a major molecular response was significantly higher with dasatinib versus imatinib (16% versus 4%, respectively; P = 0.038). Treatment failure was lower and progression-free survival higher in patients receiving dasatinib versus imatinib (P < .001), although the duration of benefit is not known because of the brief follow-up period.

Superficial oedema and fluid retention were more common in patients receiving imatinib, and pleural effusion was more common with dasatinib. Grade 3 to 4 non-hematologic toxicity was minimal. Cytopenias were more frequent and severe with dasatinib.

Author’s conclusions: ‘Dasatinib represents a safe and effective therapy for CP CML resistant to conventional imatinib doses with improved cytogenetic and molecular response rates and progression-free survival relative to high-dose imatinib.’

Source: http://bloodjournal.hematologylibrary.org/cgi/content/abstract/109/12/5143
NOTE: A preliminary study presented at ASCO this year suggested that dasatinib mayshow promising clinical benefit as first-line treatment of chronic-phase (CP) chronic myelogenous leukemia (CML) http://www.asco.org/portal/site/ASCO/menuitem.34d60f5624ba07fd506fe310ee37a01d/?vgnextoid=76f8201eb61a7010VgnVCM100000ed730ad1RCRD&vmview=abst_detail_view&confID=47&abstractID=31679