New tyrosine kinase inhibitors may represent new standard in chronic-phase CML

Major molecular responses are more common with the next generation of tyrosine kinase inhibitors as first-line options compared with imatinib for the treatment of newly diagnosed patients with chronic myelogenous leukemia (CML). Two separate studies confirmed superior response rates with dasatinib and nilotonib versus the current first-line standard imatinib.

As presented by Hagop Kantarjian, MD, chairman and professor, department of leukemia, University of Texas M.D. Anderson Cancer Center, Houston, at the annual meeting of the American Society of Clinical Oncology in Chicago, dasatinib, 100 mg once daily, was compared with imatinib, 400 mg once daily, in 519 newly diagnosed patients with Philadelphia chromosome-positive (Ph+) CML in the chronic phase in the randomized study known as DASISION (Dasatinib versus Imatinib Study in Treatment-naïve CML).

The rates of confirmed complete cytogenetic response (defined as disappearance of Ph+ cells on 2 consecutive bone marrow samples) at 12 months were 83% in the patients assigned to dasatinib compared with 72% in those randomly assigned to imatinib (

P

=.0011).

Fewer patients in the dasatinib arm discontinued treatment (15.5%) than in the imatinib arm (18.6%).

Updated results from the Evaluating Nilotinib Efficacy and Safety in Clinical Trials of Newly Diagnosed (ENESTnd) were also presented here. In the study, 846 newly diagnosed patients with CML in the chronic phase were randomized to 1 of 3 treatments: nilotinib, 300 mg twice daily; nilotinib, 400 mg twice daily; or imatinib, 400 mg once daily, until disease progression.

A major molecular response at a median follow-up of 18.5 months was achieved by 69% of patients assigned to nilotinib, 300 mg twice daily; 63% assigned to nilotinib, 400 mg twice daily, and 36% assigned to imatinib, said Richard A. Larson, professor of medicine and director of the leukemia program, University of Chicago Medical Center.

The differences in major molecular response between nilotinib and imatinib were maintained at a median of 24 months of follow-up (86%, 88%, and 48%, respectively).

Both dasatinib and nilotinib are more potent than imatinib at inhibiting BCR-ABL kinase, said the investigators. Because increased inhibition of BCR-ABL kinase correlates with better complete cytogenetic response, “longer follow-up of first-line dasatinib may demonstrate better long-term outcomes than imatinib and should become first-line therapy for newly diagnosed patients with CML,” said Dr. Kantarjian, in commenting on DASISION.