I lead a research program to improve outcomes for patients with chronic myeloid leukaemia (CML). We aim to identify poor risk patients and test new treatment strategies to reduce adverse outcomes. In good risk patients we aim to reduce the need for lifelong drug dependency. Through a combination of clinical trials, innovative correlative studies, and strong scientific collaborations, my team will continue to improve outcomes for CML patients globally.
Characterisation Of A New Poor-Risk Sub-Category Of Chronic Phase Chronic Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$609,320.00
Summary
The introduction of targeted therapy for chronic myeloid leukaemia (CML) has resulted in excellent responses for many patients. However, some 30-40% of patients respond very poorly to this therapy and therapeutic advances are urgently needed to improve response in these patients. In order to better treat these poor risk patients we aim, in this project, to develop a greater understanding of their disease, and from this identify specific cellular targets for future drug treatment/combination ther ....The introduction of targeted therapy for chronic myeloid leukaemia (CML) has resulted in excellent responses for many patients. However, some 30-40% of patients respond very poorly to this therapy and therapeutic advances are urgently needed to improve response in these patients. In order to better treat these poor risk patients we aim, in this project, to develop a greater understanding of their disease, and from this identify specific cellular targets for future drug treatment/combination therapy.Read moreRead less
Optimising Outcomes In Chronic Myeloid Leukaemia Through Rational Drug Selection Using Predictive Assay Results And Maximising Treatment Free Remissions
Funder
National Health and Medical Research Council
Funding Amount
$193,596.00
Summary
Although outcomes in chronic myeloid leukaemia are generally excellent, a number of important questions remain. In this grant, we propose to i) personalise the selection of frontline treatment for newly diagnosed patients, using biomarkers which can predict treatment response; ii) improve the probability of cure in patients aiming to stop their treatment, and iii) use ultra-sensitive molecular tests for disease detection to predict risk of disease relapse.
Chronic Myeloid Leukaemia: Changing The Treatment Paradigm
Funder
National Health and Medical Research Council
Funding Amount
$1,162,778.00
Summary
Most patients with chronic myeloid leukaemia achieve excellent responses to therapy but need therapy for life. We have pioneered the concept that some patients can cease their therapy and not relapse (treatment free remission –TFR). By studying the immune system and the leukaemic stem cells we will determine why TFR is possible for some, but not all patients. This holds the key to improving the rate of TFR, thus moving the CML goal from disease control to cure.
Assessment Of Markers Of Genomic Instability For The Prediction Of Treatment Response In Chronic Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$590,086.00
Summary
The success of therapy for patients with chronic myeloid leukaemia depends on close monitoring during therapy for early recognition of pending relapse, and the selection of appropriate treatment if drug resistance occurs. This project aims to identify patients at the start of therapy who are at risk of treatment failure by investigating their genetic profile. An increased frequency of gene mutations may indicate that patients require more aggressive therapy to achieve an optimal response.
Chronic myeloid leukaemia was almost always fatal before the development of imatinib a decade ago, the first tyrosine kinase inhibitor (TKI) developed to treat a human cancer. There are now more potent TKIs that are effective in cases of resistance to imatinib. The challenge now is to optimise the achievement of remissions using these drugs and convert CML into a curable condition. This will be the focus of my NHMRC Practitioner Fellowship over the next 5 years.
Development Of A Treatment Algorithm For Kinase Inhibitor Therapy In CML.
Funder
National Health and Medical Research Council
Funding Amount
$527,761.00
Summary
Chronic myeloid leukaemia has become a highly treatable condition since targeted therapy became available. There are now 3 highly effective drugs available, imatinib, nilotinib and dasatinib. We are developing drug sensitivity assays that can be used to predict response to these 3 drugs. We propose that these assays could be used to individualise therapy to ensure that the optimal drug can be provided for each patient from diagnosis to provide a cost-effective customized approach to therapy.
Defining Genomic Mechanisms Associated With Treatment Response, Drug Resistance And Early Blast Crisis In Chronic Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
Chronic myeloid leukaemia is a fatal disease if untreated. Most patients now survive with new drugs, but some still rapidly die. I aim to understand these differences by investigating the genetic makeup of patients at diagnosis. Some may have gene mutations that prevent drugs from working effectively. Mutations will be detected using technology that can search more than 30,000 genes at the same time. This work could lead to improved survival for more patients by finding new targets for therapy.
Determining The Prerequisites For The Achievement Of Treatment-free Remission In Chronic Myeloid Leukaemia To Facilitate The Development Of New Therapeutic Approaches With Curative Intent
Funder
National Health and Medical Research Council
Funding Amount
$1,318,775.00
Summary
Chronic myeloid leukaemia (CML) can usually be treated effectively with long-term tyrosine kinase inhibitor (TKI) therapy. Remarkably, rare patients who achieve excellent responses can stop treatment altogether without relapsing. Detailed studies of these patients in terms of their genetic background, the biology of their leukaemia and their immune response may help us understand how this is possible, leading to new therapeutic approaches to make treatment-free remission more widely achievable.
Individualising Tyrosine Kinase Inhibitor Therapy In CML To Facilitate Successful Treatment Free Remission
Funder
National Health and Medical Research Council
Funding Amount
$376,449.00
Summary
This project will determine the optimal therapy for patients with chronic myeloid leukaemia (CML), matching the most appropriate drug to the individual patient, based on each patient's unique biology, thereby maximising the chance of cure. Furthermore, this project will develop novel highly sensitive tests for the presence of residual disease, even if undetectable by current techniques. This will enable crucial, timely treatment changes to be made with curative intent.