Tyrosine Kinase Inhibitor Therapy Discontinuation for Patients with Chronic Myeloid Leukaemia in Clinical Practice

Abstract

Purpose In chronic myeloid leukaemia, tyrosine kinase inhibitor treatment is traditionally given continuously for life. However, these drugs produce excellent responses for many patients, and this is accompanied by survival that is close to normal. This has prompted studies of whether it is possible to stop treatment, thus achieving a treatment-free remission (TFR). Recent Findings Most TFR studies have focussed on abrupt cessation in patients with long-standing deep remissions, but recent data suggest that more gradual treatment de-escalation may improve TFR success, and that it may be possible to extend TFR attempts to patients who are in stable major molecular response but not necessarily MR4. Summary Further data are badly needed on TFR for patients whose remission is less than stable MR4 and on the importance of prior interferon-alpha treatment. Funding TFR trials in a disease with such an excellent outlook is an increasing challenge.

Tyrosine kinase inhibitor treatment discontinuation in chronic myeloid leukemia: patient views

“…In the case of patients who discontinued TKI treatment side effects might have been related to the occurrence of a withdrawal syndrome [1,2]. Although being considered mostly low grade, these effects cause considerable discomfort and affect a patients' QoL [1,2,8,18]. Similar to other studies [20][21][22][23][24][25], in the present survey patients rated the absence of side effects the most important benefit of TKI treatment discontinuation.…”

“…Patients eligible for TKI treatment discontinuation suffer from side effects resulting from their TKI use. In the case of patients who discontinued TKI treatment side effects might have been related to the occurrence of a withdrawal syndrome [1,2]. Although being considered mostly low grade, these effects cause considerable discomfort and affect a patients' QoL [1,2,8,18].…”

“…This group of drugs now includes imatinib, dasatinib, nilotinib, bosutinib, and ponatinib. Five years of TKI treatment has been found to result in a deep molecular response (DMR) in over 50% of patients with the percentage generally increasing with each year of treatment [1,2]. At diagnosis the average age of European patients is about 56 years [3,4].…”

“…However, clinical trial data obtained in patients using the first and second generation TKI's imatinib, dasatinib and nilotinib show that about 50% of CML patients with a sustained DMR may discontinue TKI treatment without a molecular relapse to maintain a lasting treatment-free remission (TFR). Relapse mostly occurs within the first 3-12 months after discontinuation but relapsed patients generally regain the DMR status shortly after TKI treatment resumption [1,2,10,11]. Clinical study data also indicate that in patients with a failed discontinuation attempt, a second attempt may still be successful [12][13][14].…”

No sex-related difference in achievement of treatment-free remission following treatment with tyrosine kinase inhibitors in chronic myeloid leukemia

“…However, the results of a long-term follow-up of the STIM study showed no patient sex-related differences in the achievement of TRF [4]. In addition, there have been no reports showing sex-related differences in the achievement of TRF in past studies where TKI was discontinued [5]. Although our study also showed no significant difference between male (3/9 [33.3%]) and female, (7/17 [41.2%]), the TFR rate was rather higher in female [1].…”