Minimal residual disease-based effect and long-term outcome of first-line dasatinib combined with chemotherapy for adult Philadelphia chromosomepositive acute lymphoblastic leukemia

J. H. Yoon, H. Y. Yhim, J. Y. Kwak, J. S. Ahn, D. H. Yang, J. J. Lee, S. J. Kim, J. S. Kim, S. J. Park, C. W. Choi, H. S. Eom, S. K. Park, S. Y. Choi, S. H. Kim, D. W. Kim, S. Lee

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    33 Citations (Scopus)

    Abstract

    Background: The use of imatinib combined with chemotherapy has demonstrated improved outcome in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). However, a substantial proportion of patients continue to die as a result of disease progression. Patients and methods: We assessed the minimal residual disease (MRD)-based effect and long-term outcome of firstline incorporation of dasatinib (100 mg once daily) into chemotherapy alternatively for adults with Ph-positive ALL. The primary end point was the major molecular response (MMR) rate by the end of the second dasatinib cycle. Patients with a donor proceeded to allogeneic stem cell transplantation (SCT) as early as possible. MRD monitoring was centrally evaluated by real-time quantitative polymerase chain reaction (4.5-log sensitivity) using bone marrow samples. Results: Fifty-one patients (median age, 46 years) were enrolled and treated with this strategy. After the first dasatinib cycle, 50 patients (98.0%) achieved complete remission (CR). By the end of the second dasatinib cycle, 46 (93.9%) of 49 assessable patients had persistent CR, and 38 (77.6%) had MMR (32.7%) or undetectable MRD (44.9%). On the basis of the MRD kinetics by this time point, the numbers of early-stable, late, and poor molecular responders were 23 (46.9%), 15 (30.7%), and 11 (22.4%), respectively. Thirty-nine patients (76.5%) underwent allogeneic SCT in CR1. After a median follow-up of 54 months, the 4-year cumulative incidence of relapse and disease-free survival (DFS) rate for all patients were 30.0% and 52.0%, respectively, and the corresponding outcomes among those receiving allogeneic SCT in CR1 were 20.5% and 64.1%, respectively. Poor molecular responders had a higher risk of relapse and DFS than those of early-stable molecular responders. Conclusion: This dasatinib-based protocol was effective for achieving a good quality molecular response and durable DFS in adults with Ph-positive ALL. Trial registration: clinicaltrials.gov, NCT01004497.

    Original languageEnglish
    Pages (from-to)1081-1088
    Number of pages8
    JournalAnnals of Oncology
    Volume27
    Issue number6
    DOIs
    Publication statusPublished - 2016 Jun 18

    Keywords

    • Acute lymphoblastic leukemia
    • Allogeneic stem cell transplantation
    • Dasatinib
    • Minimal residual disease
    • Philadelphia chromosome

    ASJC Scopus subject areas

    • Hematology
    • Oncology

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