Severe adverse events by tyrosine kinase inhibitors decrease survival rates in patients with newly diagnosed chronic-phase chronic myeloid leukemia.
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.
['Ota|Shuichi|S|http://orcid.org/0000-0002-3631-244X', 'Matsukawa|Toshihiro|T|', 'Yamamoto|Satoshi|S|', 'Ito|Shinichi|S|', 'Shindo|Motohiro|M|', 'Sato|Kazuya|K|', 'Kondo|Takeshi|T|', 'Kohda|Kyuhei|K|', 'Sakai|Hajime|H|', 'Mori|Akio|A|', 'Takahashi|Tohru|T|', 'Ikeda|Hiroshi|H|', 'Kuroda|Hiroyuki|H|', 'Haseyama|Yoshihito|Y|', 'Yamamoto|Masaki|M|', 'Sarashina|Takeo|T|', 'Yoshida|Makoto|M|', 'Kobayashi|Ryoji|R|', 'Nishio|Mitsufumi|M|', 'Ishihara|Toshimichi|T|', 'Hirayama|Yasuo|Y|', 'Kakinoki|Yasutaka|Y|', 'Kobayashi|Hajime|H|', 'Fukuhara|Takashi|T|', 'Imamura|Masahiro|M|', 'Kurosawa|Mitsutoshi|M|']
D000293:Adolescent D000328:Adult D000368:Aged D000369:Aged, 80 and over D000970:Antineoplastic Agents D002648:Child D002675:Child, Preschool D000069439:Dasatinib D005260:Female D016044:Fusion Proteins, bcr-abl D015973:Gene Expression Regulation, Leukemic D006801:Humans D000068877:Imatinib Mesylate D015466:Leukemia, Myeloid, Chronic-Phase D008297:Male D008875:Middle Aged D047428:Protein Kinase Inhibitors D011743:Pyrimidines D012189:Retrospective Studies D016019:Survival Analysis D016896:Treatment Outcome
adverse events tyrosine kinase inhibitor chronic myeloid leukemia dasatinib nilotinib imatinib