Patients who have not been taking a TKI for long enough (3–5 years) and those who do not have a deep enough molecular remission are not eligible for TFR. It is important that these patients understand why they cannot attempt TFR, and that CML is a potentially fatal blood cancer; therefore continuing with daily TKI treatment is vital to keep their cancer in remission. We should be clear that TFR is only attempted in patients for whom it is believed to be safe, based on extensive clinical trials. Many patients will have to wait until they have taken TKI for long enough and have a deep enough remission.
For patients who want or need to alter their treatment, dose reduction or a treatment holiday can be considered.
Dose reduction can be considered for patients who do not fit the criteria for TFR but experience side effects with TKIs. Generally, reducing the dose of TKI is known to ameliorate side effects, but this should not be at the risk of disease relapse. In the DESTINY trial, patients who had been on the same TKI (imatinib, nilotinib or dasatinib) for 3 years and were in MR3 were eligible to halve their dose for a year, followed by TFR. During the half-dose phase, the molecular relapse-free survival rate was 93% and all of these patients went on to TFR. Patients reported that most side effects improved within the first 3 months of the half-dose phase.
Treatment holiday. Some patients can be given a deliberate treatment holiday of a few days, or possibly weeks, in order to be free from side effects for a special occasion, or if they are unwell for other reasons. Treatment is restarted after a short break. However, longer treatment holidays are not recommended. Patients who want to become pregnant should be counselled about the need for a planned approach, and the need to meet the criteria for attempting TFR.
Patients may also be considered for regular treatment holidays of 2 days a week (e.g. weekends). The Phase III DasaHIT trial, which is currently recruiting patients on dasatinib, is investigating whether molecular remission rates and toxicity profiles are affected by regular treatment holidays.
