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Does BCR-ABL Transcript Subtype Affect Response to Nilotinib in CML?

By: Lauren Harrison, MS
Posted: Thursday, September 17, 2020

Even when patients are appropriately treated with nilotinib in the first-line setting, those with chronic-phase chronic myeloid leukemia (CML) who have an expression of the BCR-ABL e13a2 transcript tend to have lower rates of deep molecular responses. This research was conducted by Pascale Flandrin-Gresta, MD, of the Centre Hospitalier Universitaire de Saint-Etienne, France, and colleagues and was published in Oncotarget.

The team analyzed 114 patients with newly diagnosed CML from 5 different regions in France who were treated with front-line nilotinib. All patients included had an expression of either the e14a2 or e13a2 transcript. The patients were analyzed retrospectively, and their response to therapy was based on European LeukemiaNet recommendations. Patients were followed for a median of 49 months. Among this cohort, 55.3% of patients expressed e14a2, whereas, in the other cohort, 44.7% expressed e13a2. Patients were treated with 600 mg of nilotinib daily for a median of 42 months and 49 months in the e14a2 and e13a2 groups, respectively.

Complete hematologic and complete cytogenetic responses were similar between the two groups. However, patients who expressed the e13a2 transcript had a significantly lower rate of major molecular response at 12 months (50.1%) as compared with patients who expressed the e14a2 transcript (66.7%). The cumulative incidence of major molecular response was 100% in the e14a2 group and 84.1% in the e13a2 group. The major molecular response was achieved in a median of 6.7 months among the group expressing e14a2 as compared with 17.1 months among the group expressing e13a2.

The estimated overall 5-year survival rates among patients in the e14a2 group were 95.6% and 100% in the e13a2 group, and the 5-year event-free survival rates were 72.5% and 66.8% in these groups. Using multivariate analysis, the study authors found that a high platelet count (> 300 g/L) was the only factor that predicted better major molecular response rates.

Disclosures: The study authors reported no conflicts of interest.



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