Blood cancers

Novel predictor of treatment-free remission in CML

Tuesday, 13 Nov 2018

Dr Naranie Shanmuganathan,  a leukaemia fellow at the Royal Adelaide Hospital and Clinical Research fellow at the South Australian Health and Medical Research Institute has been awarded the ASH-HSANZ Abstract Achievement Award for work, due to be presented at the 60th ASH Annual Meeting in San Diego next month. We sat down with her to talk about her research. 

Congratulations on your award! can you describe the aim of this project in 10 words?

To identify the predictors of treatment-free remission in CML in the Adelaide cohort.

What have you discovered so far?

We have identified that the rates of treatment-free remission (TFR) success in the Adelaide cohort are similar to the published data despite the majority of our patients not being enrolled in a specific stopping study. Not only have we confirmed that the duration of deep molecular response, defined as MR4.5 (BCR-ABL1 < 0.0032% IS) in our institution, as being an important predictor of TFR success; corroborating existing data from the important TFR studies. However the most important and somewhat novel finding was that patients with a particular BCR-ABL1 transcript, the e14a2 transcript, were more likely to experience TFR success.

What aspect of this research interests you the most?

In two decades, the landscape of CML therapy has significantly changed, especially since the discovery and introduction of the first-generation tyrosine kinase inhibitor (TKI), imatinib. Patients went from requiring chemotherapy and stem cell transplantation as their only option for long-term survival to single agent oral therapy with imatinib, dramatically improving survival outcomes. However patients were still required to remain on therapy indefinitely. The concept of TFR was developed to test whether patients with excellent long-term molecular outcomes could potentially cease therapy, success that has now been proven by multiple clinical trials. Our project has helped identify which patients are most likely to successfully cease TKI in a TFR attempt, which is something that can easily be translated into clinical practice.

What are the potential clinical implications for patients with CML?

Identifying the predictors of TFR will potentially assist in selecting the patients who are most likely to successfully cease TKI. It will also assist in counselling patients that are keen to attempt TFR when as clinicians, we can present published data and figures that can support our recommendations.

How long before this work impacts patient care?

Fortunately, this data is something that can be directly translated into the CML clinic very easily.

What’s your Holy Grail – the one thing you’d like to achieve in your research career?

I would like to successfully complete my PhD, which is still going to take a number of years. Thankfully I have been fortunate to have the support and assistance of my clinical unit, my peers (both clinicians and researchers) and my supervisors; maximising my opportunities of success.

What is your biggest research hurdle?

Time – finding enough time to do everything I need to do, both clinically and in research, which I know is a skill gained through experience.

What else are you working on?

Currently, I am working on identifying genomic events that characterise CML, attempting to differentiate which mutations confer a poorer prognostic outcome. Ultimately the aim is to refine current prognostic risk models in CML, incorporating both genomic data with clinical and laboratory information to further assist in optimising CML therapy selection.

Who has inspired you in work or life?

My family has been my biggest supporters and my inspiration to always try and find answers to the questions we ask.


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