Treatment-free remission is emerging as a realistic aim for most long-term survivors of chronic myeloid leukaemia, according to Professor Tim Hughes, an internationally-renowned clinician and researcher from the Royal Adelaide Hospital.

Delivering the Carl de Gruchy oration, Professor Hughes said research on CML had been “frustratingly unproductive” during the 1990s.

“Everything changed in 1999 when Brian Druker presented the early findings of the phase I trial of imatinib, the first tyrosine kinase inhibitor (TKI), in patients with advanced CML,” he said.

Through a fortunate combination of a motivated group of collaborators in Australia and New Zealand, strong links with key decision-makers in the pharmaceutical industry and the availability of an excellent assay developed in Adelaide to measure the response to therapy, Adelaide found itself at the centre in the early trials of imatinib and other TKIs.

For example, the Adelaide laboratory led an international effort to standardise BCR-Abl assays and developed the OCT-1 assay of kinase inhibition.

Three TKIs are now available for CML: imatinib, nilotinib and dasatinib. While the two newer agents are more potent inhibitors of BCR-Abl activity and far less prone to the development of resistance, they are generally more toxic.

“In unselected groups of patients they have not achieved any improvements in survival as CML-related deaths have been balanced by an increase in non-CML-related deaths,” Professor Hughes said.

“We now need to identify the patients in whom the balance between benefit and risk is most favourable.

“The challenge is to use these new agents in the most effective way with a focus on rational and customised approach to drug selection, as well as basing management decisions on the best quality assays to determine drug sensitivity and emerging resistance.”

There is still considerable scope to improve the outcomes of patients with chronic phase CML. Groups which do relatively poorly include those who develop blast crisis despite receiving TKI therapy, patients who suffer significant organ damage and, rarely, those who die from TKI toxicity.

“A ‘precision medicine’ approach to therapy is the pathway we will need to take to make further improvements,” Professor Hughes said.

A recent important step has been the realisation that up to 20% of patients currently achieve a ‘deep response’ and can stop TKI treatment, raising hopes for treatment-free remission in a higher proportion of cases.