An Australian-led research program aims to substantially increase the number of people with chronic myeloid leukaemia who can safely stop therapy and remain in remission.
Australian researchers are targeting one of the next big challenges in chronic myeloid leukaemia: helping more patients achieve sustained treatment-free remission rather than requiring lifelong therapy.
Professor Tim Hughes, clinical director of the Precision Cancer Medicine Theme at SAHMRI and professor of haematology at Adelaide University, will lead a five-year research program investigating why some patients with chronic myeloid leukaemia (CML) can safely discontinue therapy while others cannot.
The program, supported by an NHMRC Investigator Grant, will bring together national and international collaborators and use laboratory studies and clinical trials to investigate the barriers preventing treatment-free remission (TFR).
It builds on more than a decade of research led by Professor Hughes demonstrating that CML therapy does not necessarily need to be lifelong in patients who achieve a sufficiently deep molecular response.
Although sustained treatment-free remission has become a major goal of CML therapy, only about one in three patients currently achieve it, according to the researchers. Most patients therefore continue treatment to maintain control of their disease.
“While current therapies have transformed CML into a manageable chronic illness, lifelong therapy remains the norm for most patients,” Professor Hughes said.
“This imposes substantial burdens, including side effects that impair quality of life and the ongoing risk of drug resistance.”
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The success of tyrosine kinase inhibitor therapy has dramatically changed the clinical landscape of CML, shifting the research question from simply controlling the disease towards identifying which patients can ultimately live without ongoing treatment.
The new research program will focus on understanding the biological factors that determine whether treatment-free remission can be achieved and maintained.
According to the research team, the key question is increasingly why some people can stop CML treatment without their disease returning while others remain dependent on therapy.
A series of laboratory investigations and clinical trials will explore those barriers and assess potential approaches to increase the proportion of patients able to successfully discontinue treatment.
Immunotherapy is among the strategies researchers believe could help expand the pool of patients capable of achieving sustained TFR.
“Immunotherapy may hold the key to further expanding the pool of people capable of achieving and maintaining TFR, but we are exploring several promising approaches,” Professor Hughes said.
The program reflects the evolution of CML treatment over recent decades. With effective therapies capable of achieving durable disease control, researchers can increasingly focus on the mechanisms underlying deep molecular response, treatment withdrawal, and subsequent relapse.
A better understanding of those mechanisms could ultimately allow clinicians to identify patients most likely to successfully stop therapy and develop interventions that enable more people to reach that point.
For patients, successful treatment-free remission potentially means avoiding the cumulative burden of years of medication and its associated adverse effects while maintaining control of their CML.
Professor Hughes said advances in the field had created an opportunity to investigate the biology of treatment response and relapse in much greater depth.
“We’ve reached a point where scientific advances allow us to ask deeper questions about response and relapse, that’s where the next breakthroughs will come from.”
