Dasatinib discontinuation in patients with chronic-phase chronic myeloid leukemia and stable deep molecular response: the DASFREE study

Abstract

Treatment-free remission (TFR) in patients with chronic myeloid leukemia in chronic phase (CML-CP) is considered a feasible option, especially with the ability of second-generation tyrosine kinase inhibitors to induce higher rates of sustained deep molecular response (DMR). DASFREE is an open-label, single-arm, multicenter phase II trial assessing TFR after dasatinib discontinuation in patients with CML-CP (N = 84). At 2 years, TFR was 46% in all patients. Multivariate analyses revealed statistically significant associations between 2-year TFR and duration of prior dasatinib (≥median; p = .0051), line of therapy (first line; p = .0138), and age (>65 years; p = .0012). No disease transformation occurred, and the most common adverse events experienced off treatment were musculoskeletal (observed in 30 patients); however, dasatinib withdrawal events were reported in nine patients (11%) by the investigator. Overall, these findings support the feasibility of discontinuing dasatinib for patients with CML-CP in sustained DMR in the first line and beyond.

Keywords:

• Dasatinib
• imatinib
• deep molecular response
• treatment-free remission
• major molecular response
• CML-CP

Acknowledgments

The authors thank the patients who participated in this study and the clinical study teams. The authors also thank the protocol manager, Renuka Gurnani. Medical writing and editorial support were provided by Jessica Franciosi, PhD, Andrea Lockett, and Joshua Safran of StemScientific (Lyndhurst, NJ, USA), an Ashfield Company, funded by Bristol-Myers Squibb.

Disclosure statement

N. P. S. has received research funding from ARIAD, Bristol-Myers Squibb, Daiichi-Sankyo, and Pfizer. V. G. has served as a consultant to, received research funding from, or served on the board of directors/advisors of Bristol-Myers Squibb, Incyte, Novartis, and Pfizer. A. J. and S. L. declare no conflicts to disclose. S. S. has received research funding from Bristol-Myers Squibb and Novartis, and honoraria from Bristol-Myers Squibb, Incyte, Novartis, and Pfizer. D. R. has served as a consultant to Bristol-Myers Squibb and Novartis, and received honoraria from Bristol-Myers Squibb, Incyte, Novartis, and Pfizer. F. M. has received research funding and honoraria from ARIAD, Bristol-Myers Squibb, Novartis, and Pfizer. M. Y. L. declares no conflicts to disclose. M. T. G. has served on the speakers’ bureaus of Bristol-Myers Squibb, Incyte, Novartis, and Pfizer. FP has received honoraria from and served on the speakers’ bureau of Novartis. F. N. has served as a consultant to Bristol-Myers Squibb, received honoraria from and served on the speakers’ bureaus of Bristol-Myers Squibb and Incyte, and received research funding from Novartis. M. J. M. has served as a consultant to Bristol-Myers Squibb. O. S. and P. M. are employees of Bristol-Myers Squibb. J. H. L. has served as a consultant to, received research funding from, or served as an advisor to ARIAD, Bristol-Myers Squibb, Novartis, and Pfizer.

Data availability statement

BMS policy on data sharing may be found at https://www.bms.com/researchers-and-partners/independent-research/data-sharing-request-process.html.

Additional information

Funding

This study was sponsored and funded by Bristol-Myers Squibb.