1.Literature Analysis of the Selection of Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia Patients with BCR-ABL35INS Mutation
Meiling YAN ; Meng ZHANG ; Lin HUANG ; Yueping JIA ; Yi ZHANG ; Wanyu FENG ; Hui’er GAO
China Pharmacy 2019;30(12):1675-1678
OBJECTIVE: To provide reference for reasonable selection of tyrosine kinase inhibitors (TKI) in chronic myeloid leukemia (CML) patients with BCR-ABL35INS mutation. METHODS: Using “BCR-ABL insertional mutation” “ABL1 35ins mutation” “BCR-ABL c.1423_1424ins35” “ABL1 p.C475Tyrfs*11” as keywords, retrieved from CNKI, Wanfang database, Medline and COSMIC database, BCR-ABL35INS mutation CML patients were summarized and analyzed in respects of general information and treatment (treatment plan, patient compliance and drug withdrawal), therapeutic effect (molecular biological mitigation and disease progress) and safety data (ADR) during 2007-2018. RESULTS: Totally 9 related literatures were included, involving 70 patients with BCR-ABL35INS mutation, all of them were foreign cases. Among them, 39 cases were male and 31 cases were female, with a median age of 49.2 years. The median time from the diagnosis of CML to the detection of BCR-ABL35INS mutation was 19 months. After detecting gene mutation, 39 cases were treated with imatinib (initial dose of 400 mg, po, once a day), and molecular biological remission was achieved in 5 patients (12.9%); 15 cases (38.5%) had molecular biological response but had disease progression; 8 patients (20.5%) had no response. Seventeen patients were treated with dasatinib (100 mg, po, once a day or 2 divided dose), and 8 cases (47.1%) achieved molecular biological response. Twenty-one patients were treated with nilotinib (400 mg, po, 2 divided dose), and 3 patients (14.3%) achieved molecular biological response; 2 patients achieved molecular biological response, but the disease progressed. Seven, three and seven of these patients stopped taking drugs due to adverse reactions, accounting for 17.9%, 17.6% and 33.3% respectively. All the ADRs were classified as grade 3-4 of the National Cancer Institute’s Common Terminology Criteria for Adverse Events, and most of them were hematological toxicity. CONCLUSIONS: CML patients with BCR-ABL35INS mutation are less likely to achieve molecular response on imatinib therapy but are more sensitive to dashatinib. In the course of treatment, we should strengthen the monitoring of blood system and other related indicators to ensure the safety and effectiveness of drug use.