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Posted by on Feb 25, 2018 in Leukemia | 0 comments

In a nutshell

This study reviewed evidence on the safety and effectiveness of stopping TKI therapy in patients with chronic myeloid leukemia (CML). Authors concluded that discontinuing TKI therapy is safe and effective in many patients with deep molecular response.

Some background

Tyrosine kinase inhibitors (TKIs) is a first-line treatment for CML. TKIs work by blocking proteins called tyrosine kinases. Many patients achieve deep molecular response with TKI therapy (showing no more genetic abnormalities in the bone marrow). Deep molecular response is associated with a near-normal life expectancy. However, many patients lose this response once TKI therapy is stopped. It can be regained quickly when restarting TKI therapy. Patients usually undergo a life-long duration of TKI therapy. Patients may want to stop treatment due to side effects and costs.

Methods & findings

In an early study on TKI discontinuation, 100 CML patients in the chronic (early) phase showed undetectable disease for at least 2 years before stopping TKI therapy. Patients had undergone at least 3 years of treatment. At 24 months after the end of treatment, 43% patients were still in remission (no sign of disease). At 60 months, it was 38%. 95% of relapses (return of disease) occurred in the first 7 months with no relapses reported after 22 months. No cases of disease progression were observed.

Studies have shown that a longer duration of TKI therapy predicts for better outcomes after discontinuation. However, further studies are needed. It is recommended that patients should have achieved deep molecular response to treatment before attempting discontinuation. Patients with major molecular response are at higher risk of relapse compared to those with deep molecular response.

Having high-risk disease, such as a high Sokal risk score, increases the chance after stopping treatment. Blood tests measuring lymphocyte counts (a type of white blood cell) can also help predict outcomes after discontinuation. Specifically, patients with a high number of natural killer cells (a type of lymphocyte) are more likely to stay in remission.

Outcomes of discontinuing second-generation TKIs, such as nilotinib (Tasigna) and dasatinib (Sprycel), are similar compared to discontinuing first-generation TKIs, such as imatinib (Glivec). In a study of 190 CML patients stopping nilotinib after 2 years, 51.6% maintained their treatment response at 48 weeks. However, patients receiving a second-generation TKI are more likely to achieve deep molecular response and are eligible to stop.

Whether a second TKI discontinuation attempt can be successful after a failed first attempt was investigated in 67 patients. 44% of patients maintained their treatment response and did not restart therapy after the second discontinuation.  

The bottom line

Authors concluded that discontinuing TKI therapy is safe and effective in many patients with deep molecular response. The authors estimated that for 100 newly diagnosed patients, about half will achieve deep molecular response. Of those, about half will successfully stop treatment. Based on this, about three-quarters of CML patients will require life-long TKI therapy.

Published By :

Current hematologic malignancy reports

Date :

Sep 25, 2017

Original Title :

Chronic Myeloid Leukemia-the Promise of Tyrosine Kinase Inhibitor Discontinuation.

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