Shuichi Ota1, Toshihiro Matsukawa2, Satoshi Yamamoto3, Shinichi Ito4, Motohiro Shindo5, Kazuya Sato6, Takeshi Kondo7, Kyuhei Kohda8, Hajime Sakai9, Akio Mori10, Tohru Takahashi11, Hiroshi Ikeda12, Hiroyuki Kuroda13, Yoshihito Haseyama14, Masaki Yamamoto15, Takeo Sarashina16, Makoto Yoshida17, Ryoji Kobayashi18, Mitsufumi Nishio19, Toshimichi Ishihara20, Yasuo Hirayama21, Yasutaka Kakinoki22, Hajime Kobayashi23, Takashi Fukuhara24, Masahiro Imamura1, Mitsutoshi Kurosawa25. 1. Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan. 2. Department of Hematology, Kushiro Rosai Hospital, Kushiro, Japan. 3. Department of Hematology, Sapporo City General Hospital, Sapporo, Japan. 4. Department of Hematology, Hakodate Municipal Hospital, Hakodate, Japan. 5. Department of Hematology, Asahikawa Medical University, Asahikawa, Japan. 6. Department of Hematology/Oncology, Asahikawa Kosei Hospital, Asahikawa, Japan. 7. Faculty of Medicine and Graduate School of Medicine, Department of Hematology, Hokkaido University, Sapporo, Japan. 8. Department of Hematology, Japanese Red Cross Asahikawa Hospital, Asahikawa, Japan. 9. Department of Hematology, Teine Keijinkai Hospital, Sapporo, Japan. 10. Department of Hematology, Aiiku Hospital, Sapporo, Japan. 11. Department of Hematology, Tenshi Hospital, Sapporo, Japan. 12. Department of Hematology, Sapporo Medical University, Sapporo, Japan. 13. Department of Hematology, Steel Memorial Muroran Hospital, Muroran, Japan. 14. Department of Hematology, Tonan Hospital, Sapporo, Japan. 15. Department of Pediatrics, Sapporo Medical University, Sapporo, Japan. 16. Department of Pediatrics, Asahikawa Medical University, Asahikawa, Japan. 17. Department of Pediatrics, Japanese Red Cross Asahikawa Hospital, Asahikawa, Japan. 18. Department of Hematology/Oncology for Children and Adolescent, Sapporo Hokuyu Hospital, Sapporo, Japan. 19. Department of Hematology and Oncology, NTT East Japan Sapporo Hospital, Sapporo, Japan. 20. Department of Hematology, Kin-ikyo Chuo Hospital, Sapporo, Japan. 21. Department of Hematology, Higashisapporo Hospital, Sapporo, Japan. 22. Department of Hematology, Asahikawa City Hospital, Asahikawa, Japan. 23. Department of Hematology, Obihiro Kosei Hospital, Obihiro, Japan. 24. Palliative Care Center, Sapporo Kosei Hospital, Sapporo, Japan. 25. Department of Hematology, Hokkaido Cancer Center, Sapporo, Japan.
Abstract
OBJECTIVE: This multicenter cooperative study aimed to analyze the adverse events (AEs) associated with tyrosine kinase inhibitors (TKIs) used as initial treatment for chronic-phase chronic myeloid leukemia (CML-CP) and their impact on outcome. METHODS: We retrospectively evaluated 450 patients with CML-CP who received TKIs between 2004 and 2014. RESULTS: The 5-year overall survival (OS) and event-free survival (EFS) rates were 95.1% and 89.0%, respectively. Patients with comorbidities (46.4%) and aged ≥60 years (50.4%) at diagnosis had significantly inferior OS to those without comorbidities and aged <60. Patients achieved higher rates of major molecular response (MMR) at 6 and 12 months after initial treatment with dasatinib or nilotinib compared to imatinib, but final MMR rates were almost the same. Sixty-six percent of patients required treatment modifications from first-line TKI therapy; the main reasons were AEs (48.4%) and failure (18%). Grade III-IV AEs in first-line TKI therapy were significantly correlated to inferior OS/EFS compared to grade 0-II AEs. CONCLUSION: Although long-term outcomes were similar in CML-CP patients treated with each TKI regardless of first-line TKI selection, severe AEs in first-line TKI therapy decreased their survival rates. Early change in TKIs is recommended, when faced with severe AEs of specific TKIs.
OBJECTIVE: This multicenter cooperative study aimed to analyze the adverse events (AEs) associated with tyrosine kinase inhibitors (TKIs) used as initial treatment for chronic-phase chronic myeloid leukemia (CML-CP) and their impact on outcome. METHODS: We retrospectively evaluated 450 patients with CML-CP who received TKIs between 2004 and 2014. RESULTS: The 5-year overall survival (OS) and event-free survival (EFS) rates were 95.1% and 89.0%, respectively. Patients with comorbidities (46.4%) and aged ≥60 years (50.4%) at diagnosis had significantly inferior OS to those without comorbidities and aged <60. Patients achieved higher rates of major molecular response (MMR) at 6 and 12 months after initial treatment with dasatinib or nilotinib compared to imatinib, but final MMR rates were almost the same. Sixty-six percent of patients required treatment modifications from first-line TKI therapy; the main reasons were AEs (48.4%) and failure (18%). Grade III-IV AEs in first-line TKI therapy were significantly correlated to inferior OS/EFS compared to grade 0-II AEs. CONCLUSION: Although long-term outcomes were similar in CML-CP patients treated with each TKI regardless of first-line TKI selection, severe AEs in first-line TKI therapy decreased their survival rates. Early change in TKIs is recommended, when faced with severe AEs of specific TKIs.