Hawk Kim1, SooHyun Kim2, Hyeoung-Joon Kim3, Yeo-Kyeoung Kim3, Jae-Yong Kwak4, Ho-Young Yhim4, Sung-Hyun Kim5, Young Rok Do6, Sukjoong Oh7, Sung-Eun Lee8, Saengsuree Jootar9, Jiu Wei Cui10, Dong-Wook Kim11. 1. Division of Hematology, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea. 2. Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea. 3. Chonnam National University Hwasun Hospital, Hwasun-gun Jeollanam-do, Korea. 4. Chonbuk National University Hospital, Jeollabuk-do, Korea. 5. College of Medicine, Dong-A University, Busan, Korea. 6. School of Medicine, Keimyung University Dongsan Medical Center, Daegu, Korea. 7. Department of Hematology and Oncology, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul, Korea. 8. Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea; Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. 9. Ramathibodi Hospital, Bangkok, Thailand. 10. The First Hospital of Jilin University, Changchun, China. 11. Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea; Catholic Hematology Hospital, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. Electronic address: dwkim@catholic.ac.kr.
Abstract
INTRODUCTION: BCR-ABL1 mutations require consideration during second-line tyrosine kinase inhibitor selection for patients with chronic myeloid leukemia (CML). The present retrospective analysis compared the frequency of BCR-ABL1 mutations in Asian and white patients in whom imatinib therapy had failed. PATIENTS AND METHODS: A nonstudy cohort (76 Asian patients from community clinical practices) and 2 study cohorts (29 Asian and 352 white patients from dasatinib phase II and III clinical trials) were identified. RESULTS: In the nonstudy cohort, 80 mutations were identified; the most frequent was T315I (15%), followed by phosphate-binding loop mutations E255K (11%), G250E (10%), and Y253H (10%). Asian patients had a greater proportion of T315I and phosphate-binding loop mutations compared with the white patients. The nonstudy cohort was less likely to have multiple mutations compared with either study cohort. Single mutations highly resistant to dasatinib, nilotinib, and bosutinib were more frequent in the Asian than in the white cohorts. CONCLUSION: These results suggest that mutational analysis findings will be invaluable for choosing an appropriate second-line tyrosine kinase inhibitor in Asia.
INTRODUCTION: BCR-ABL1 mutations require consideration during second-line tyrosine kinase inhibitor selection for patients with chronic myeloid leukemia (CML). The present retrospective analysis compared the frequency of BCR-ABL1 mutations in Asian and white patients in whom imatinib therapy had failed. PATIENTS AND METHODS: A nonstudy cohort (76 Asian patients from community clinical practices) and 2 study cohorts (29 Asian and 352 white patients from dasatinib phase II and III clinical trials) were identified. RESULTS: In the nonstudy cohort, 80 mutations were identified; the most frequent was T315I (15%), followed by phosphate-binding loop mutations E255K (11%), G250E (10%), and Y253H (10%). Asian patients had a greater proportion of T315I and phosphate-binding loop mutations compared with the white patients. The nonstudy cohort was less likely to have multiple mutations compared with either study cohort. Single mutations highly resistant to dasatinib, nilotinib, and bosutinib were more frequent in the Asian than in the white cohorts. CONCLUSION: These results suggest that mutational analysis findings will be invaluable for choosing an appropriate second-line tyrosine kinase inhibitor in Asia.
Authors: Chen Chen; Na Xu; Xuejie Jiang; Waner Wu; Xuan Zhou; Liang Liu; Jixian Huang; Changxin Yin; Rui Cao; Libin Liao; Dan Xu; Yuming Zhang; Qifa Liu; Xiaoli Liu Journal: Nan Fang Yi Ke Da Xue Xue Bao Date: 2019-03-30
Authors: E Dianne Pulte; Haiyan Chen; Lauren S L Price; Ramadevi Gudi; Hongshan Li; Olanrewaju O Okusanya; Lian Ma; Lisa Rodriguez; Jonathon Vallejo; Kelly J Norsworthy; R Angelo de Claro; Marc R Theoret; Richard Pazdur Journal: Oncologist Date: 2022-03-04 Impact factor: 5.837