The impact of time to response to treatment on the outcomes of patients with accelerated-phase chronic myeloid leukemia

This study aimed to investigate the impact of time to response to treatment on the outcomes of patients with accelerated-phase chronic myeloid leukemia. 

This study concluded that an early response to treatment is strongly associated with long-term survival in these patients.  

Tyrosine kinase inhibitors (TKI) are a type of targeted therapy that can be used for treating chronic myeloid leukemia (CML). Imatinib (Gleevec), dasatinib (Sprycel), and nilotinib (Tasigna) are TKIs.  Most patients with CML are diagnosed with chronic-phase (CP). TKIs are the standard treatment for these patients. However, 5-10% of patients with CMP present with accelerated-phase (AP) at diagnosis. There is only limited data about the outcomes of TKIs in these patients. 

The time to treatment response (TTR) differs for every patient. In patients with CP-CML, TTR is associated with patient outcomes. However, the impact of TTR on the outcomes for patients with AP-CML are still unknown.  

This study involved 75 patients with AP-CML. Patients had at least one feature of AP. 33 patients were treated with imatinib and 42 received a second-generation tyrosine kinase inhibitor (2G-TKI). Of the 42, 19 received dasatinib and 23 received nilotinib.  

The impact of molecular (MR) and cytogenetic responses (CyR) at early time points (3 and 6 months) on the rates of overall CyR and MR, overall survival (OS), event-free survival (EFS), and failure-free survival (FFS) were measured. MR measures the level of BCR-ABL (cancer gene) present in the blood. CyR measures the amount of cells without the Philadelphia chromosomes (abnormal leukemia gene) present in the bone marrow.  

After an average of 96 months, the overall rate of complete CyR was 79%. The rate of major MR was 71%. The rate of deep (long-lasting) MR was 59%.  

The 3-year OS rate was 94% for patients who achieved a major CyR at 3 months compared to 75% for patients who did not achieve a major CyR at 3 months. The 3-year transformation-free survival (TFS) rate was 98% for the group who had a major CyR at 3 months. This was compared to 73% for patients who did not achieve major CyR at 3 months. 

The 3-year EFS rate was 93% for the group who had a major CyR at 3 months compared to 42% for the patients who did not achieve a major CyR at 3 months. The 3-year FFS rate was 83% for the patients who had a major CyR at 3 months compared to 25% for the patients who did not achieve a major CyR at 3 months.  

67% of patients who achieved sustained deep MR had achieved a major CyR at 3 months. 

This study concluded that an early response at 3 and 6 months is a strong determinant of long-term survival for patients with AP-CML. 

This study did not evaluate whether switching to another TKI after 3-6 months in patients with a poorer response leads to better outcomes. Further studies are needed.