Outcomes of patients with chronic phase chronic myeloid leukemia (CML-CP) after discontinuation of frontline ponatinib therapy

Abstract

Considering the risk of arterio-thrombotic adverse events (AEs), ponatinib trials in previously untreated chronic myeloid leukemia chronic phase (CML-CP) were terminated. We conducted a retrospective CML-CP outcome study of patients who discontinued frontline-ponatinib. Among 51 patients who received frontline ponatinib, 38 discontinued because of FDA request and 13 due to AEs. At ponatinib discontinuation, all patients remained in CP with deepest response being CCyR, n = 7; PCyR, n = 4; MMR, n = 14; MR4.5, n = 26. Of the four patients in PCyR at ponatinib discontinuation, two improved response to CCyR on subsequent TKI. Of seven patients, in CCyR at discontinuation, five improved response to MMR or deeper, one was inevaluable, and another lost response due to treatment noncompliance. With a median follow-up of 39 months, 3-year EFS and OS were 92% and 96%, respectively, indicating favorable long-term outcomes. The cardiac/vascular system AEs with subsequent TKI occurred in patients with prior similar events on ponatinib. AEs occurred up to 9 months post-ponatinib.

Keywords:

• Ponatinib
• chronic myeloid leukemia
• frontline
• chronic phase
• outcomes

Acknowledgments

J.C. provided conception and design of the study, collection, analysis, and interpretation of data, provided patient data for study, writing and revising the manuscript, and final review and approval of the manuscript. P.B. and P.J. have contributed equally toward this manuscript and are first coauthors for this article; they contributed equally to data collection and analysis, and writing, reviewing, and approving the manuscript. H.K., G.B., G.G.M., S.V., T.K., N.J., and E.J. provided patient data for study, revision of the manuscript, and final review and approval of the manuscript. A.A. provided review of the manuscript.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2019.1617862.

Additional information

Funding

This study was supported by University of Texas MD Anderson Cancer Center Support Grant [P30 CA16672] and award P01 CA049639 from the National Cancer Institute (NCI). Jorge Cortes is the recipient of a grant from the NCI [P01 CA049639].