CML patient motivation for TFR remission attempts highlighted
medwireNews: Researchers have reviewed the feasibility of, and motivation for, treatment-free remission (TFR) in chronic myeloid leukaemia (CML) patients with a deep molecular response (MR) to tyrosine kinase inhibitor (TKI) therapy.
Lauren Caldemeyer and Luke Akard, from the Franciscan St Francis Hospital and Health Centers in Indianapolis, Indiana, USA, acknowledge that that majority of studies so far have looked at TFR in patients with a deep MR to imatinib but a few studies have suggested this is also possible with nilotinib or dasatinib.
And although TFR has not been tested for the second- or later-line agents ponatinib and bosutinib, study findings indicate that patients may achieve the deep MR required for a TFR attempt with both these TKIs.
The authors highlight the impact of side effects as a motivator for attempting TFR, noting that long-term TKI use is thought to be associated with long-term cardiopulmonary or atherosclerotic adverse events (AEs) that affect both mortality and morbidity, especially with second-generation agents.
In particular, they cite reports of serious cardiovascular AEs such as ischaemic heart disease, peripheral artery disease and ischaemic cerebrovascular events, as well as pulmonary hypertension and pleural effusion.
“With long-term therapy, even low-grade AEs can have significant impacts on patients’ quality of life”, the authors add in Leukemia & Lymphoma, citing health survey reports of AEs such as low-grade muscle cramps, musculoskeletal pain, fatigue, oedema and gastrointestinal symptoms.
Such AEs are thought to be at least as common in patients given imatinib as in those given second-generation TKIs, research suggests
However, while AEs may resolve in patients during TFR, the authors note that the EURO-SKI results were the first to suggest the possibility of an imatinib withdrawal symptom, with musculoskeletal pain reported in around 30% of patients within 6 weeks of stopping treatment.
“The potential for a TKI withdrawal syndrome requires further investigation in ongoing TFR trials”, say Caldemeyer and Akard.
“The alleviation or avoidance of chronic or long-term AEs provides a compelling reason for attempting TFR; however, TFR should be attempted only in a clinical trial where patients receive frequent molecular monitoring and can reinitiate TKI therapy promptly following molecular relapse.”
Other motivations for attempting TFR include a reduced financial burden, convenience or a wish to become pregnant, the researchers comment.
A patient’s willingness to attempt TFR may also be affected by their physician’s recommendation, the patient’s perception of TFR being safe, their risk of relapse and a guarantee of adequate monitoring for relapse, they add, noting that surveys have suggested that around two-thirds of patients might consider an attempt given the right assurances.
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