BCR‐ABL1 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

摘要

The present study aimed to assess the clinical impact of BCR‐ABL1 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‐ABL1 transcript levels of CML‐CP patients (n = 258; median age, 43 [range, 18‐81] years) treated with various tyrosine kinase inhibitors (TKIs) 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‐ABL1 transcripts for achieving major molecular responses (MMRs) 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‐ style="fixed-case">ABL1 transcripts at 4 weeks (very early style="fixed-case">MR; style="fixed-case"> VEMR), patients with style="fixed-case">VEMR achieved higher 3‐month style="fixed-case">EMR and 4‐week style="fixed-case">VEMR significantly associated with higher cumulative incidences of 5‐year style="fixed-case">MMR (89.1% vs 72.3%; P < 0.001) and 5‐year deep molecular response ( style="fixed-case">DMR) (56.5% vs 29.4%; P = 0.001). Furthermore, event‐free survival ( style="fixed-case">EFS)‐a (93.0% vs 84.8%; P = 0.068) and style="fixed-case">EFS‐b (71.1% vs 57.9%; P = 0.061) by 5 years were also marginally significant. style="fixed-case">VEMR and 3‐month style="fixed-case">EMR were achieved in 89 patients, with significantly superior outcomes. In multivariate analyses, lower leukocyte count (P = 0.008) and frontline second‐generation style="fixed-case">TKI therapy size (P < 0.001) were significantly associated with style="fixed-case">VEMR achievement, but not baseline style="fixed-case">BCR‐ style="fixed-case">ABL1 level and style="fixed-case">CML duration. In conclusion, the 4‐week style="fixed-case">BCR‐ style="fixed-case">ABL1 transcript levels including style="fixed-case">VEMR could be important to predict long‐term outcomes and may provide additional information about innate intrinsic sensitivity to style="fixed-case">CML among individuals.