Blood cancers

Treatment free remission closer to a reality in CML


Impressive and sustained success in using tyrosine kinase inhibitors (TKIs) to treat chronic myeloid leukemia (CML), and trials showing some patients can safely stop therapy without relapse, has prompted a push to take the practice into the mainstream setting.

Leading haematologists also want to see the establishment of guidelines to define the best strategies for identifying and managing patients most suited to achieving treatment free remission (TFR).

Writing in a perspective in the American Society of Hematology’s Blood journal, Dr David Ross and Dr Tim Hughes, both haematologists with SA Pathology, School of Medicine, University of Adelaide, Adelaide, Australia, and also at the South Australian Health and Medical Research Institute said: “The dramatic success of tyrosine kinase inhibitors (TKIs) has led to the widespread perception that chronic myeloid leukaemia (CML) has become another chronic disease, where lifelong commitment to pharmacologic control is the paradigm.”

“Recent trials demonstrate that some CML patients who have achieved stable deep molecular response can safely cease their therapy without relapsing. Furthermore, those who are unsuccessful in their cessation attempt can safely re-establish remission after restarting their TKI therapy.

“Based on the accumulated data on TFR, we propose that it is now time to change our approach for the many CML patients who have achieved a stable deep molecular response on long-term TKI therapy,” they wrote.

Speaking to the limbic, Dr Ross said not all patients would be suitable to be offered a TFR attempt, especially those who were unwilling or unable to comply with frequent monitoring.

“If you’ve got someone who is unreliable and already has difficulty taking their tablets there is a risk there, but I don’t expect that to be a real problem,” he said.

There might also be some psychological impact of being off TKI therapy, the authors suggested.

“Some patients might experience significant anxiety relating to concerns of relapse, and almost 50% of patients in an Italian survey said that they would be afraid of losing their disease response,” they wrote.

“It is also possible that patients who are offered a TFR attempt might misinterpret this as permission to reduce or omit doses.”

Dr Ross said the decision to attempt TFR would have to be carefully discussed and aimed at the patients who have had the best possible response to TKIs and “kept that response for a significant amount of time”.

“I don’t think people should be pushed into it unless they want to,” he said.

Dr Ross said he expected some patients would welcome the opportunity to attempt TFR, especially those who experienced moderate to severe TKI-related side effects. There was also a growing awareness of other uncommon, but potentially serious, risks of long-term TKI treatment that may emerge after months or years.

 

“I think there are a lot of patients who will welcome the opportunity, I think there is a groundswell of interest both among patients and among doctors.

“I think it’s been going on now for long enough that people are thinking it’s not some weird idea that comes and goes – it’s here to stay.”

He said there was now need to establish criteria for safe and appropriate TKI cessation, and clinical trials would identify the best strategies.

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