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Posted by on Aug 21, 2018 in Leukemia | 0 comments

In a nutshell

This study evaluated the effectiveness and safety of second-generation tyrosine kinase (TK) inhibitors after imatinib (Gleevec) therapy in children and adolescents with chronic myeloid leukemia (CML). The authors concluded that second-generation TK inhibitors may be a viable first-line treatment option for these patients.

Some background

Second-generation TK inhibitors have become a part of standard first-line treatment for chronic phase CML. These include drugs like nilotinib (Tasigna) or dasatinib (Sprycel). This type of treatment is a targeted therapy. This treatment blocks cancer cell survival. This leads to cancer cell death.

Previous studies have shown that nilotinib and dasatinib are effective in adult patients with CML. The effectiveness and safety of these drugs following imatinib therapy in children and adolescents with CML remains under investigation.

Methods & findings

This study included the records of 152 Japanese children and adolescents with chronic phase CML. All patients received imatinib as first-line (primary) therapy.

20.39% of patients switched to nilotinib (10.53%) or dasatinib (9.87%) as second-line treatment after an average of 25 months of imatinib therapy. This was due to either poor treatment response or side effects with imatinib. Switches due to side effects occurred significantly earlier than switches due to poor treatment response (7 months vs. 33 months). Patients were followed-up for an average of 64 months. 

Response to treatment improved in 63% of patients who switched from imatinib to nilotinib or dasatinib. 45.2% of patients had a complete response (no signs of CML). 48.3% of patients had a partial response (some signs or symptoms of CML remain). 25.8% of patients later switched again to another TK inhibitor.

Most reported side effects were mild to moderate. Significantly more patients treated with nilotinib experienced jaundice (yellow appearance of the skin and eyes because of too much of the pigment bilirubin in the blood) compared to patients treated with dasatinib (33% vs. 0%). More patients treated with dasatinib experienced muscle or joint pain compared to patients treated with nilotinib (80% vs. 33.3%).

The bottom line

The authors concluded that second-generation TK inhibitors may be a viable first-line treatment option for children and adolescents with chronic phase CML.

The fine print

This study was retrospective, meaning it looked back in time to analyze data. This study only included Japanese patients, so the results may not be applicable to all patients.

This study analyzed data for only 31 out of 152 patients who switched from imatinib to another TK inhibitor. This patient population is quite small. Larger studies are needed to confirm these results.

Published By :

Pediatric blood & cancer

Date :

Aug 07, 2018

Original Title :

Sequential use of second-generation tyrosine kinase inhibitors following imatinib therapy in pediatric chronic myeloid leukemia: A report from the Japanese Pediatric Leukemia/Lymphoma Study Group.

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