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, Jinseok 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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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
Article numbermdw123
Pages (from-to)1081-1088
Number of pages8
JournalAnnals of Oncology
Volume27
Issue number6
DOIs
Publication statusPublished - 2016 Jun 18

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Residual Neoplasm
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Drug Therapy
Philadelphia Chromosome
Stem Cell Transplantation
Disease-Free Survival
Recurrence
Dasatinib
Disease Progression
Real-Time Polymerase Chain Reaction
Survival Rate
Bone Marrow
Tissue Donors
Incidence

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology

Cite this

Yoon, J. H. ; Yhim, H. Y. ; Kwak, J. Y. ; Ahn, J. S. ; Yang, D. H. ; Lee, J. J. ; Kim, S. J. ; Kim, Jinseok ; Park, S. J. ; Choi, C. W. ; Eom, H. S. ; Park, S. K. ; Choi, S. Y. ; Kim, S. H. ; Kim, D. W. ; Lee, S. / Minimal residual disease-based effect and long-term outcome of first-line dasatinib combined with chemotherapy for adult Philadelphia chromosomepositive acute lymphoblastic leukemia. In: Annals of Oncology. 2016 ; Vol. 27, No. 6. pp. 1081-1088.
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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.",
author = "Yoon, {J. H.} and Yhim, {H. Y.} and Kwak, {J. Y.} and Ahn, {J. S.} and Yang, {D. H.} and Lee, {J. J.} and Kim, {S. J.} and Jinseok Kim and Park, {S. J.} and Choi, {C. W.} and Eom, {H. S.} and Park, {S. K.} and Choi, {S. Y.} and Kim, {S. H.} and Kim, {D. W.} and S. Lee",
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Yoon, JH, Yhim, HY, Kwak, JY, Ahn, JS, Yang, DH, Lee, JJ, Kim, SJ, Kim, J, Park, SJ, Choi, CW, Eom, HS, Park, SK, Choi, SY, Kim, SH, Kim, DW & Lee, S 2016, 'Minimal residual disease-based effect and long-term outcome of first-line dasatinib combined with chemotherapy for adult Philadelphia chromosomepositive acute lymphoblastic leukemia', Annals of Oncology, vol. 27, no. 6, mdw123, pp. 1081-1088. https://doi.org/10.1093/annonc/mdw123

Minimal residual disease-based effect and long-term outcome of first-line dasatinib combined with chemotherapy for adult Philadelphia chromosomepositive acute lymphoblastic leukemia. / Yoon, J. H.; Yhim, H. Y.; Kwak, J. Y.; Ahn, J. S.; Yang, D. H.; Lee, J. J.; Kim, S. J.; Kim, Jinseok; Park, S. J.; Choi, C. W.; Eom, H. S.; Park, S. K.; Choi, S. Y.; Kim, S. H.; Kim, D. W.; Lee, S.

In: Annals of Oncology, Vol. 27, No. 6, mdw123, 18.06.2016, p. 1081-1088.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Minimal residual disease-based effect and long-term outcome of first-line dasatinib combined with chemotherapy for adult Philadelphia chromosomepositive acute lymphoblastic leukemia

AU - Yoon, J. H.

AU - Yhim, H. Y.

AU - Kwak, J. Y.

AU - Ahn, J. S.

AU - Yang, D. H.

AU - Lee, J. J.

AU - Kim, S. J.

AU - Kim, Jinseok

AU - Park, S. J.

AU - Choi, C. W.

AU - Eom, H. S.

AU - Park, S. K.

AU - Choi, S. Y.

AU - Kim, S. H.

AU - Kim, D. W.

AU - Lee, S.

PY - 2016/6/18

Y1 - 2016/6/18

N2 - 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.

AB - 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.

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