Early BCR-ABL1 Reduction Is Predictive of Better Event-free Survival in Patients With Newly Diagnosed Chronic Myeloid Leukemia Treated With Any Tyrosine Kinase Inhibitor

• Published in: Clinical lymphoma, myeloma and leukemia Vol. 16; pp. S96 - S100
• Main Authors: Fava, Carmen, Rege-Cambrin, Giovanna, Dogliotti, Irene, Gottardi, Enrico, Berchialla, Paola, Di Gioacchino, Bruno, Crasto, Francesca, Lorenzatti, Roberta, Volpengo, Alessandro, Daraio, Filomena, Fantino, Cristina, Saglio, Giuseppe
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-08-2016
• Subjects: Adult; Aged; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Chronic myeloid leukemia; Early molecular response; Female; Follow-Up Studies; Fusion Proteins, bcr-abl - genetics; Gene Expression Regulation, Leukemic - drug effects; Halving time; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - diagnosis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - mortality; Male; Middle Aged; Molecular monitoring; Neoplasm Staging; Prognosis; Prognostic factors; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Retrospective Studies; Survival Analysis; Time Factors; Treatment Outcome; Early molecular response; Molecular monitoring; Chronic myeloid leukemia; Halving time; Prognostic factors
• ISSN: 2152-2650; 2152-2669
• DOI: 10.1016/j.clml.2016.03.008

The clinical prognostic factors during treatment are very important in chronic myeloid leukemia. An early molecular response and the halving time of BCR-ABL1 might be highly predictive of the outcome. A retrospective analysis of a cohort of 50 patients showed the importance of a very early molecular response in identifying subjects with favorable outcomes, using ABL1 as the control gene for the analysis.
An early molecular response has a strong predictive value in chronic myeloid leukemia (CML). Recently, the halving time (velocity of early BCR-ABL1 transcript elimination) has been shown to represent an additional prognostic index. Our objective was the evaluation of the prognostic significance of the 3-month point in our population. We retrospectively collected BCR-ABL1 transcript data at different time points, events, and survival data of patients with CML treated at the Division of Hematology, San Luigi Hospital, University of Turin, Turin, Italy. Of 71 patients diagnosed from January 2005 to March 2015 in our center and treated with front-line tyrosine kinase inhibitors (imatinib, nilotinib and dasatinib), we selected those who had undergone a molecular evaluation at 3 months. The event-free survival (EFS) by the median follow-up time was the primary endpoint. The data from 50 patients with CML chronic phase were analyzed. Overall, 34 of the 50 patients (68%) had a transcript ≤ 10% at 3 months. Of those in the > 10% group, 63% had experienced an event compared with 12% in the ≤ 10% group by the median follow-up point (P < .001). The halving time threshold for discriminating between EFS was 17 days. None of the patients with a transcript > 10% at 3 months had a halving time of ≤ 17 days. Patients with BCR-ABL1 ≤ 10% and a halving time of ≤ 17 days had significantly better EFS than that of patients with BCR-ABL1 ≤ 10% and a halving time > 17 days and of patients with BCR-ABL1 > 10% (96% group 1 vs. 60% group 2 vs. 27% group 3; P < .001). Irrespective of the tyrosine kinase inhibitor used, the prognosis was significantly superior for patients with BCR-ABL1 ≤ 10% and halving time of ≤ 17 days. Our data revealed that the use of ABL1 as a control gene is reliable for the determination of the halving time in the clinical setting and highlight the importance of measuring the BCR-ABL1 transcript at CML diagnosis.