Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Aug 1;126(15):3438-3447.
doi: 10.1002/cncr.32940. Epub 2020 May 27.

Low-dose tyrosine kinase inhibitors before treatment discontinuation do not impair treatment-free remission in chronic myeloid leukemia patients: Results of a retrospective study

Emilie Cayssials  1   2   3 , Jose Torregrosa-Diaz  1   2 , Pilar Gallego-Hernanz  1 , Florence Tartarin  2 , Thomas Systchenko  1 , Natacha Maillard  1 , Déborah Desmier  1 , Antoine Machet  1 , Emmanuel Fleck  4 , Anne Corby  4 , Carine Motard  5 , Guillaume Denis  6 , André Herbelin  3 , Jean-Marc Gombert  3 , Lydia Roy  7 , Stéphanie Ragot  2 , Xavier Leleu  1   2 , François Guilhot  2 , Jean-Claude Chomel  8
Affiliations
Free article

Low-dose tyrosine kinase inhibitors before treatment discontinuation do not impair treatment-free remission in chronic myeloid leukemia patients: Results of a retrospective study

Emilie Cayssials et al. Cancer. .
Free article

Abstract

Background: Long-term treatment-free remission (TFR) represents a new goal for chronic myeloid leukemia (CML). In clinical practice, tyrosine kinase inhibitor (TKI) dose reductions can be considered a means of preventing adverse effects and improving quality of life. We hypothesized that administration of low-dose TKIs before treatment discontinuation does not impair TFR in patients with CML who have a deep molecular response (DMR, ≥MR4 ).

Methods: We conducted a retrospective analysis of 77 patients with CML who discontinued treatment with TKIs. Twenty-six patients had been managed with low-dose TKIs before stopping treatment. Patients were to be exposed to TKIs for ≥5 years and to low-dose TKIs for ≥1 year and in DMR for ≥2 years. The loss of major molecular response (MMR) was considered a trigger for restarting therapy.

Results: In the low-dose group, 61.5% of patients received second-generation TKIs, and dose reduction was ≥50% for 65.4% of patients. With a median follow-up of 61.5 months, TFR at 12 months was 56.8% in the full-dose TKI group and 80.8% in the low-dose group, and TFR at 60 months was 47.5% and 58.8%, respectively. The median time to molecular recurrence (≥MMR) from TKI discontinuation in the entire cohort was 6.2 months. All patients quickly achieved MMR after resuming TKI therapy. Results appear independent of both dose reduction and potential pretreatment with interferon-α.

Conclusion: This retrospective study shows that TFR was not impaired by low-dose TKI regimens before TKI cessation in Patients with CML. Nevertheless, prospective randomized clinical trials must be undertaken to analyze the probability of successful TFR in patients managed with TKI dose de-escalation strategies before TKI discontinuation.

Keywords: TKI de-escalation; chronic myeloid leukemia; treatment discontinuation; treatment-free remission; tyrosine kinase inhibitors.

PubMed Disclaimer

Comment in

References

    1. Hehlmann R, Lauseker M, Saußele S, et al. Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants. Leukemia. 2017;31:2398-2406. doi:10.1038/leu.2017.253
    1. Steegmann JL, Baccarani M, Breccia M, et al. European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia. Leukemia. 2016;30:1648-1671. doi:10.1038/leu.2016.104
    1. Experts in Chronic Myeloid Leukemia. The price of drugs for chronic myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs: from the perspective of a large group of CML experts. Blood. 2013;121:4439-4442. doi:10.1182/blood-2013-03-490003
    1. Mahon F-X. Treatment-free remission in CML: who, how, and why? ASH Educ Program Book. 2017;2017:102-109. doi:10.1182/asheducation-2017.1.102
    1. Copland M. Is there a role for dose modification of TKI therapy in CML? Curr Hematol Malig Rep. 2019;14:337-345. doi:10.1007/s11899-019-00524-w

MeSH terms

Substances

LinkOut - more resources