Anxiety and depression associated with tyrosine kinase inhibitor discontinuation in patients with chronic myeloid leukemia
ABL tyrosine kinase inhibitors (TKIs) significantly changed the prognosis of patients with chronic myeloid leukemia (CML), and clinical trials demonstrated that TKIs can be discontinued in approximately 50% of patients after a period of deep molecular response (DMR). However, in some patients, TKI discontinuation leads to anxiety and depression. Here, we analysed the incidence of anxiety and depression in patients who stop TKI therapy.
Anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale (HADS) in 32 patients with CML. The survey periods were at TKI discontinuation, at 1, 6, 12, and 24 months and at reintroduction of TKIs. The HADS score at the initial TKI discontinuation was compared between patients within and outside clinical trials. Treatment-free remission (TFR) rates outside clinical trials were evaluated.
The HADS scores were significantly higher at TKI reintroduction after molecular relapse than at the initial TKI discontinuation (at the initiation of stopping TKIs vs. at reintroduction of TKIs, 8.47 ± 5.53 vs. 1.67 ± 2.26; p = 0.0003). The TFR rate at 12 months after stopping TKIs outside clinical trials was 55.6%. The HADS score at the initial TKI discontinuation did not differ between patients within and outside clinical trials.
Stopping TKIs outside clinical trials is feasible if the guidelines for stopping are followed and an adequate monitoring system is available. Discontinuation of TKIs requires adequate management of anxiety and depression.
KeywordsChronic myeloid leukemia The Hospital Anxiety and Depression Scale Discontinuation of treatment ABL tyrosine kinase inhibitor
Compliance with ethical standards
Conflict of interest
SK received research funding from Bristol-Myers Squibb, Pfizer, Otsuka Pharmaceutical, Novartis and Ohara Pharmaceutical, and received honoraria from Bristol-Myers Squibb, Pfizer, Otsuka Pharmaceutical and Novartis.
- 5.Rousselot P, Charbonnier A, Cony-Makhoul P et al (2014) Loss of major molecular response as a trigger for restarting tyrosine kinase inhibitor therapy in patients with chronic-phase chronic myelogenous leukemia who have stopped imatinib after durable undetectable disease. J Clin Oncol 32:424–430CrossRefGoogle Scholar
- 7.Mahon FX, Richter J, Guilhot J et al (2014) Interim analysis of a pan European stop tyrosine kinase inhibitor trial in chronic myeloid leukemia: the EURO-SKI study. ASH 2014 Abstract 151Google Scholar
- 19.Guidelines for clinical practice of hematological malignancies, Japanese society of Hematology. http://www.jshem.or.jp/gui-hemali/1_4.html. Accessed 21 February 2018
- 27.Hematologic Cancer. Division of Hematology, Respiratory Medicine and Oncology. http://www.saga-hor.jp/main/176.html. Accessed 21 Feb 2018