Patient-guided dose reduction of tyrosine kinase inhibitors in chronic myeloid leukaemia (RODEO): a prospective, multicentre, single-arm study

Tyrosine kinase inhibitors have proven to be safe and effective in the
treatment of chronic myeloid leukaemia. Despite their effectiveness, TKIs are
also associated with adverse events that can decrease patients* quality of life
and increase healthcare utilization and costs. Recent studies have indicated
that dose reduction of TKIs can benefit optimal use by maintaining therapy
efficacy while reducing adverse events and medication costs and increasing
quality of life. These studies have used a one-size fits all approach and dose
reduction was initiated by the healthcare provider. However, the choice for
dose reduction can be considered as a preference sensitive decision as the
preferred treatment option is dependent on personal needs and preferences of
each individual (e.g. treatment goal and the extent of dose reduction). Thus, a
patient-centred approach is needed to meet these needs and preferences.

Primary: To assess the proportion of patients with intervention failure at 12
months after dose reduction, defined as patients who have restarted their
initial dose due to (expected) loss of major molecular response.

prospective, multicentre, single-arm study

The intervention is a patient*guided dose reduction. Patients will receive
personalised, lower TKI doses, using an online patient decision aid and decide
upon during a shared decision making consult.

A lower dose might be as therapeutically effective as standard dose. We expect
that no more than 19% of the patients will experience intervention failure
after dose reduction. Moreover, we expect that patients who restart their
initial dose will regain MMR or better again. Furthermore, it is possible to
expect some benefits with regards to patient-reported side effects, QoL,
attitudes towards medication (intake), medication adherence due to lower TKI
dose. Also, with this personalised approach, one can expect that patients*
level of distress and remorse concerning their choice for dose reduction is
low. However, investigating whether this will be true is an essential aspect of
this study and will be assessed by collecting patient-reported data.

Reducing the dose induces the risk to lose molecular response. To accurately
monitor the risk of loss of molecular response, an extra BCR-ABL1 analysis will
be performed 6 weeks after each dose reduction and 3-monthly thereafter
according to European guidelines [1]. All BCR-ABL results are seen and
authorized by the treating internist-haematologist. An increase in the BCR-ABL1
transcript levels and possible loss of response is therefore noticed
immediately. Literature show that in case of loss of MMR, resuming standard
dose allows for MMR achievement within 4 months. Therefore, dose reduction does
not endanger patients.