Early BCR-ABL1 decline in imatinib-treated patients with chronic myeloid leukemia: results from a multicenter study of the Chinese CML alliance.

Abstract

An early molecular response is spectacularly predictive of outcome in chronic myeloid leukemia (CML) and early response landmarks may identify the high-risk patients likely to be benefit from an early therapy switch. In this study, we evaluated the most relevant cutoffs for early molecular response markers (BCR-ABL1 values at 3 months, log reduction and halving time between diagnosis and 3 months) in 476 first-line imatinib-treated Chinese patients with chronic phase CML. All outcomes were significantly superior for the 324 patients with 3-month BCR-ABL1 ≤10%, so did for the 270 patients with BCR-ABL1 >0.61 log reduction. BCR-ABL1 halving time ≤22 days was identified for patients with the most favorable outcome. Moreover, the prognosis was significantly poorest for patients with both halving time >44 days and BCR-ABL1 >10%. Importantly, multivariate regression analysis demonstrated that a BCR-ABL1 log reduction calculated at 3 months of 0.61 was the only variable that significantly predicted for OS. Our results highlight the importance of rapid initial decline of BCR-ABL1 in predicting satisfactory outcome. Our data support the evidence that monitoring BCR-ABL1 values at an early time point could contribute to accurately assess response and ultimately guide clinical decisions regarding the timing of therapeutic intervention.

• Authors: Jingru Zhang, Yingqiao Wang, Jianxiang Wang, Jianda Hu, Suning Chen, Jie Jin, Ting Liu, Jianfeng Zhou, Yu Hu, Daoxin Ma, Xiaojun Huang, Chunyan Ji, Ming Hou
• Journal: Blood cancer journal (Blood Cancer J) Vol. 8 Issue 7 Pg. 61 (06 15 2018) ISSN: 2044-5385 [Electronic] United States
• PMID: 29915172 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• BCR-ABL1 fusion protein, human
• Protein Kinase Inhibitors
• Imatinib Mesylate
• Fusion Proteins, bcr-abl

Topics

• Adolescent
• Adult
• Aged
• Antineoplastic Agents (administration & dosage, adverse effects, therapeutic use)
• Female
• Fusion Proteins, bcr-abl (genetics)
• Gene Expression Regulation, Leukemic
• Humans
• Imatinib Mesylate (administration & dosage, adverse effects, therapeutic use)
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, genetics, mortality)
• Male
• Middle Aged
• Prognosis
• Protein Kinase Inhibitors (administration & dosage, adverse effects, therapeutic use)
• Survival Analysis
• Transcription, Genetic
• Treatment Outcome
• Young Adult