Long-term remission rates after treatment with second-generation tyrosine kinase inhibitors

This study examined long-term remission rates after treatment with second-generation tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML). Researchers reported that second-generation TKIs can achieve lasting remission rates up to 48 months after the end of treatment.

Targeted therapy is the standard treatment for CML. This is 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) and dasatinib (Sprycel), are often recommended as second-line treatments. In recent years, however, such second-generation TKIs have been increasingly used as primary therapy.

Treatment response in CML is measured based on patients showing few or no abnormal chromosomes (cytogenetic response) or genetic abnormalities (molecular response) in the blood or bone marrow. Major molecular remission (no abnormal chromosomes) is usually the ultimate goal of CML treatment. More studies are needed examining the long-term molecular remission rates in patients treated with second-generation TKIs.

The aim of this study was to examine whether major molecular remission can be maintained after discontinuing treatment with second-generation TKIs.

60 patients with chronic (early) phase CML were included in this study. Patients were treated with nilotinib or with dasatinib for at least 3 years either as a primary therapy or after imatinib treatment. All patients had reached major or complete molecular response and stopped treatment. The rate of patients who then maintained in remission at 12 months was analyzed. Average follow-up after treatment discontinuation was 47 months.

At 12 months, 63.3% of patients maintained major molecular response and did not require additional treatment. This was 53.6% at 48 months.

Overall, 43.3% of patients experienced relapse (on a molecular level) during the study period. The average time to molecular relapse in these patients was 4 months. The rates of molecular relapse were 35% at 12 months and 44.8% at 48 months.

After treatment discontinuation, no patients progressed towards advanced phase CML. All patients that relapsed regained either major or complete molecular response after restarting therapy.

High-risk disease and duration of previous imatinib treatment were predictors of molecular relapse. Patients who received nilotinib or dasatinib as a primary therapy or had not developed resistance (no longer responding) to imatinib were significantly more likely to maintain in molecular remission. The molecular relapse rate for these patients was 35.5% at 48 months. In contrast, the molecular relapse rate at 48 months was 76.9% for patients who had resistance to previous imatinib treatment. 

Researchers concluded that second-generation TKIs are associated with promising remission rates after discontinuing treatment. 

Larger trials are needed to confirm these preliminary results.