Examining treatment outcomes with second-line tyrosine kinase inhibitors over time

This study examined treatment outcomes in patients with chronic myeloid leukemia (CML) treated with second-line tyrosine kinase inhibitors (TKIs). Researchers concluded that treatment responses with second-line TKIs are stable over time. Patients with less favorable treatment outcomes can be identified early during therapy.

Targeted therapy is the standard first-line treatment for CML. This refers to a type of treatment that uses drugs or small molecules that block the growth and spread of cancer. TKIs are a type of targeted therapy that block enzymes called tyrosine kinases. Imatinib (Gleevac) is the TKI therapy most commonly used to treat CML. Over time, however, some patients stop responding to imatinib or have to discontinue treatment due to side effects. Second-generation TKIs, such as nilotinib (Tasigna), dasatinib (Sprycel) and bosutinib (Bosulif), may be used as second-line treatments.

Treatment response is often measured based on patients showing few or no abnormal chromosomes (cytogenetic response) or genetic abnormalities (molecular response) in the blood or bone marrow. It has been estimated that about half of patients treated with second-line TKIs achieve complete cytogenetic response. However, more studies are needed examining the long-term treatment outcomes of second-line TKIs.

The aim of this study was to examine the effectiveness of second-line TKIs after failure of imatinib.

119 patients with CML in the chronic (early) phase no longer responding to imatinib were included in this study. 91 patients were then treated with dasatinib as a second-line treatment. 25 patients received nilotinib. 3 patients were treated with bosutinib. Treatment outcomes were followed for an average of 36.3 months. 30.1% of patients were followed for more than 48 months.

62 patients (52%) discontinued their second-line TKI either due to resistance to treatment (31 patients) or due to side effects (31 patients). 57 patients were still receiving the same second-line TKI at the last follow-up.

The 4-year overall survival rate (proportion who have not died from any cause since treatment) was 81.9%. Predictors of overall survival were disease risk group and previous cytogenetic resistance to imatinib. 80.6% of patients were progression-free at 4 years. 35.3% of patients did not experience a treatment-related event such as progression, death, treatment discontinuation, or treatment failure during the 4 years.

Major molecular response rate was 32% at 4 years and the complete molecular response rate was 6.8%. The probability of being alive and showing complete cytogenetic response at 4 years was 54.4%. Patients showing greater responses (on a molecular level – 10% or less of genetically abnormal cells) at 3 months were associated with significantly better treatment outcomes compared to patients showing smaller early treatment responses. Overall survival, event-free survival, and the proportion of patients being alive and showing complete cytogenetic response at any given time point were all significantly greater.

Researchers concluded that responses to second-line TKIs are stable over time. Patients with less favorable treatment outcomes can be identified early during therapy.

Larger studies are needed to confirm these findings.