
BCR ‐ ABL 1 transcript levels at 4 weeks have prognostic significance for time‐specific responses and for predicting survival in chronic‐phase chronic myeloid leukemia patients treated with various tyrosine kinase inhibitors
Author(s) -
Song Hyeyoung,
Noh Hayeon,
Choi Soo young,
Lee SungEun,
Kim SooHyun,
Kee KyungMi,
Yoo HeaLyun,
Lee Miyoung,
Kang KiHoon,
Suh JiHyung,
Yang Seonyoung,
Jang EunJung,
Lee Jangik I.,
Kim DongWook
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1753
Subject(s) - myeloid leukemia , medicine , gastroenterology , receiver operating characteristic , abl , tyrosine kinase , immunology , receptor
The present study aimed to assess the clinical impact of BCR ‐ ABL 1 transcript levels determined at an earlier time point than the 3‐month early molecular response ( EMR ) in chronic‐phase chronic myeloid leukemia ( CML ‐ CP ) patients. BCR ‐ ABL 1 transcript levels of CML ‐ CP patients (n = 258; median age, 43 [range, 18‐81] years) treated with various tyrosine kinase inhibitors ( TKI s) were determined at 4 weeks (28 ± 3 days) and at every 3 months of treatment initiation. At 4 weeks, receiver operating characteristic curves revealed that cutoff values of BCR ‐ ABL 1 transcripts for achieving major molecular responses ( MMR s) by 12 and 60 months were 40.89% and 39.16%, respectively (95% CI , 0.658‐0.772 and 95% CI , 0.643‐0.758; P < 0.0001). With 40% of BCR ‐ ABL 1 transcripts at 4 weeks (very early MR ; VEMR ), patients with VEMR achieved higher 3‐month EMR and 4‐week VEMR significantly associated with higher cumulative incidences of 5‐year MMR (89.1% vs 72.3%; P < 0.001) and 5‐year deep molecular response ( DMR ) (56.5% vs 29.4%; P = 0.001). Furthermore, event‐free survival ( EFS )‐a (93.0% vs 84.8%; P = 0.068) and EFS ‐b (71.1% vs 57.9%; P = 0.061) by 5 years were also marginally significant. VEMR and 3‐month EMR were achieved in 89 patients, with significantly superior outcomes. In multivariate analyses, lower leukocyte count ( P = 0.008) and frontline second‐generation TKI therapy size ( P < 0.001) were significantly associated with VEMR achievement, but not baseline BCR ‐ ABL 1 level and CML duration. In conclusion, the 4‐week BCR ‐ ABL 1 transcript levels including VEMR could be important to predict long‐term outcomes and may provide additional information about innate intrinsic sensitivity to CML among individuals.