Minimal residual disease-based effect and long-term outcome of first-line dasatinib combined with chemotherapy for adult Philadelphia chromosome-positive 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, J.-S.
Park, S. J.
Choi, C.W.
Eom, H.-S.
Park, S.-K.
Choi, S.-Y.
Kim, S.-H.
Kim, D.-W.
Lee, S.

¹Department of Hematology, Catholic BMT Center
²Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul
³Division of Hematology–Oncology, Department of Internal Medicine, Chonbuk National University Medical School, Jeonju
⁴Department of Hematology–Oncology, Chonnam National University Hwasun Hospital, Jeollanamdo
⁵Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul
⁶Division of Hematology–Oncology, Department of Internal Medicine, Korea University School of Medicine, Seoul
⁷Hematologic Oncology Clinic, Center for Specific Organs Center, National Cancer Center, Goyang
⁸Division of Hematology–Oncology, Department of Internal Medicine, Soonchunhyang University School of Medicine, Bucheon, Republic of Korea

Correspondence to: Prof. Seok Lee, Department of Hematology, Catholic BMT Center, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 137-701, Republic of Korea. Tel: +82-2-2258-6055; Fax: +82-2-780-1283, E-mail: [email protected]

Received November 29, 2015

Received in revised form January 20, 2016

Accepted February 21, 2016

Annals of Oncology 27(6):p 1081-1088, June 2016. | DOI: 10.1093/annonc/mdw123

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 first-line 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.