Chromosomal abnormalities at diagnosis does not predict long-term treatment outcomes with tyrosine kinase inhibitors

This study examined whether chromosomal abnormalities at diagnosis can predict treatment outcomes with TKIs in chronic myeloid leukemia (CML). Researchers reported similar long-term treatment outcomes in patients with and without chromosomal abnormalities at diagnosis.

CML is a disease in which the bone marrow makes too many mature and immature white blood cells. It is typically a slowly progressing disease that occurs mainly during or after middle age. Certain genetic changes in CML can make it more difficult to treat. Changes in the chromosomes in blood cells, such as damaged or missing parts, are known as additional cytogenetic abnormalities (or ACA). ACA are a high-risk factor in CML. The role of ACA as a predictor of treatment outcomes with tyrosine kinase inhibitors (TKIs) is less well understood.

This study included 603 patients with chronic-phase (early-phase) CML. Of these, 5% had ACA at diagnosis. All patients received first-line therapy with a TKI. TKIs included imatinib (Gleevec), dasatinib (Sprycel), nilotinib (Tasigna), or ponatinib (Iclusig). Treatment outcomes were followed for an average of 8 years.

There are different types of treatment outcomes in CML. Cytogenetic response refers to few or no abnormal chromosomes in the blood or bone marrow. Molecular response is when there are few or no genetic abnormalities in the blood or bone marrow.

The rate of complete cytogenetic response at 6 months was significantly higher in patients without ACA compared to patients with ACA at diagnosis. However, the overall rates of cytogenetic and molecular responses were similar in both groups.

86% of patients achieved major molecular response. 69% of patients achieved a deep molecular response. Among patients without ACA, 85% achieved major molecular response and 70% achieved deep molecular response. 2 of 29 (7%) patients with ACA showed a sustained deep molecular response (maintained for 2 years with at least 5 measurements). 78 of 574 (14%) patients without ACA showed sustained deep molecular response.

ACA at diagnosis did not predict treatment outcomes at 5 years. These included transformation of disease, treatment failure, treatment-related events such as progression or death, and expected survival.

This study concluded that ACA at diagnosis is not a predictor of prognosis for patients with CML treated with a TKI.

The number of patients with ACA in this study was 29. Larger studies are needed to confirm these results.