For Dr Sun Loo, being part of an innovative clinical trial is a perfect fit. It furthers research into her field of interest – measurable residual disease (MRD), and the blood cancer she is passionate about – acute myeloid leukaemia (AML).
“AML is a moving field and I absolutely love it,” says the Melbourne-based clinical haematologist and researcher.
She is one of the main clinicians running the trailblazing AMLM26 INTERCEPT* platform trial which opened last year (late-2022). The overarching aim of the clinical trial, spearheaded by Professor Andrew Wei and led by the Australasian Leukaemia & Lymphoma Group (ALLG)**, is to find out if novel MRD-directed therapies can achieve a sustained response in patients and increase the duration of remission in early AML relapse.
Dr Loo received a 2023 PhD scholarship, co-funded by the Leukaemia Foundation and the Haematology Society of Australia and New Zealand, which she said was “incredibly important” in helping support her research linked to the AMLM26 trial.
By the time she completes her PhD in 2025, she hopes there will be “some signals from the clinical trial” regarding the effect of early treatment on response, remission, and quality of life for people with AML.
And her work doesn’t stop after her PhD. In 2026 and beyond, as the trial continues, Dr Loo’s focus then will be on summarising the findings at leading haematological conferences nationally and internationally, and reporting the outcomes of the research.
Another aspect of the trial, she says, “is to see if there are other novel MRD assessment technologies out there that we can use to study some patients on the trial, as part of correlative studies”.
And lastly, she hopes the clinical trial will “really see if we can unravel the biology of leukaemia cells at the MRD versus morphologic stage of relapse, because a lot of this is still unknown at the moment”.
Acute myeloid leukaemia and measurable residual disease
AML is a blood cancer whereby the bone marrow is overrun by immature cells, termed leukaemic blasts.
“In leukaemia, you’ve somehow developed a mutation, or some event which has caused your bone marrow to have an excess of all these immature cells,” says Dr Loo.
“It’s like you’ve got a world that’s overrun with immature babies – it’s never going to be very functional.”
Of the series of medications for AML that have become available since 2017, “some have actually changed the survival landscape of patients”.
“And in the last five years, with the advancement of technology, we’ve found better ways to detect leukaemia cells at low levels.”
Dr Loo explained that with AML, historically, the goal of treatment was to achieve complete remission, and complete remission means the assessment of a patient’s bone marrow biopsy after treatment and finding less than 5% leukaemia cells or blasts.
Conventionally this has been done by microscopy – with a haematologist sitting in the lab, counting the cells that look like blasts.
“There was never any clear finesse in how we detected leukaemia,” says Dr Loo.
“Out of 200-500 cells, how many of them look like leukaemia cells underneath the microscope? That’s how you derive the less than 5%, or 5% or more number.
“Despite treatment and attainment of complete remission, leukaemia cells can remain at 1 in 100,000-1,000,000 cells and can be a cause of relapse,” Dr Loo explains.
Rising MRD – a sign of relapse
The definition of measurable residual disease, according to Dr Loo, is “the ability to detect residual leukaemia cells below microscopy assessment using various laboratory techniques”.
“With MRD assessment, we are applying technologies which allow us to assess leukaemia down to 1 in 1 million cells,” she explains.
Dr Loo said that over the last five years “there has been an increase in internationally available recommendations of what MRD is, how to use it, why it is used, and ultimately, the prognostic implications of MRD”.
The advent of new molecular assays, with flow cytometry, means that some proportion of AML can be detected now at less than what microscopy thresholds can – at 1% or less, which has increased the type of precision-based medicine that is being used in AML. Dr Loo said some of these laboratory tests are widely available, some aren’t, and some are still under research use.
“On the other hand, the definition of morphologic relapse is when the bone marrow repopulates with leukaemic blasts at levels of 5% or more,” explains Dr Loo.
Currently, treatment of relapsed AML is initiated when morphologic relapse occurs and that is the standard practice now.
“With medications that have been approved since 2017, we’ve been using all of them for patients with frank morphologic relapse, but we’re not using them at the time that we are detecting leukaemia at the MRD stage with these new technologies,” says Dr Loo.
“There have been increasing reports of MRD-directed treatment in the past two years.”
“With this trial we are shifting the goal posts of treatment, using it a lot earlier, to when we’re starting to see the emergence of these leukaemic cells through other laboratory assays versus just microscopy and finding more than 5% blasts.
“At that time [morphologic relapse], treating patients is a lot more difficult. They usually face high rates of infection, have low blood counts, spend more time in hospital, and need more blood transfusions,” she says.
The AMLM26 INTERCEPT trial approach is to repurpose these medications, using them earlier, at the time of MRD relapse.
Preliminary data from some pilot studies, where patients were treated in MRD relapse, found that MRD response is achievable and can be done in a safe and less toxic way.
Dr Loo said the AMLM26 INTERCEPT clinical trial was the first time this was being done on a large, national scale, with novel therapies, and “will provide guidance as to what we do in the future to see whether it’s effective or not”.
“There is existing evidence that assessment of some MRD markers can precede clinical relapse by one to three months, acting as a harbinger of morphologic relapse.”
“But we haven’t got the perfect world yet,” says Dr Loo.
“We’ve got patients where you detect MRD who never relapse, and you’ve also got patients where you don’t detect MRD and they ultimately relapse.”
“So, the question is – are we measuring the right thing? Are we using the right assay to measure what needs to be measured?”
“I think all of that is undergoing advancement right now.”
About AMLM26 INTERCEPT
Dr Loo described this trial as “the first of its kind as a multi-domain, multi-arm, MRD-directed platform trial that is adaptive and precision-based in AML nationally. The platform structure permits simultaneous assessment of various novel therapies at once according to the patient’s MRD marker.”
“We’re aiming to garner proof-of-concept for the use of novel therapies in this setting, and we want to use novel targeted inhibitors as monotherapy or as combination therapies to see if it’s effective in patients with MRD failure or early morphologic relapse in AML,” explains Dr Loo.
“And the fact that we are doing a group of standard and novel molecular assays to track MRD, is with the hope of early intervention in relapsed AML.”
The goal is to assess if novel agents can induce an MRD response, prolong remission and we’ll see if there are any improved overall survival signals as well.
“The patients are able to rotate from one treatment arm to another within a platform, which prolongs their longevity on the study, and hopefully that’s also an improvement in quality of life for the patient.”
“The trial does not only comprise a treatment phase to provide treatment options for patients,” continues Dr Loo.
“There’s also a proceeding monitoring phase in order to harmonise MRD monitoring nationally and detect MRD relapse with personalised expert guidance provided by the trial’s very integral MRD Reference Committee.”
“The whole set-up of the monitoring phase is not purely to identify patients for the trial,” Dr Loo explains.
“It’s really to broaden the practise of MRD tracking. This practice is increasingly incorporated in a lot of major centres all around the world.”
“It would be very, very exciting to see, now that we’ve got many papers telling us that MRD is bad… can we do anything about it to change the fate [of relapse/remission]?
“I think that’s the biggest question now and I’m very excited to be a part of that.”
Dr Loo works closely with a lot of people on this study. They include the “extremely dedicated” ALLG team (mainly Amanda Souza, the clinical trial Project Manager; and Rev Sharma and Nadia Munsef, the Clinical Research Associates) who Dr Loo said work tirelessly to coordinate the trial and keep it running efficiently. Also, Prof. Andrew Wei (the Chief Investigator of the whole AMLM26 INTERCEPT platform trial), the members of the AMLM26 INTERCEPT Trial Management Committee (chaired by Dr Carolyn Grove), who supervises the clinical processes of the trial, the MRD Reference Committee (chaired by Professor Harry Iland AM and Associate Professor David Westerman), and the correlative research science team.
“Some of us have weekly operational meetings and we’ve been doing so for the last two years, so all of this is blood, sweat, and tears,” says Dr Loo.
“It’s just so complex, and to do it in a right way and to do it on such a large scale, there’s a lot of responsibility.”
“My role was the protocol writing, as Co-Chief Investigator of various treatment arms which are contained within the platform, and as a member of the Trial Management Committee,” she says.
Dr Loo also works with young emerging investigators, to mentor the inner workings of a clinical trial.
Background on Dr Sun Loo
When she was younger, Sun Loo was a runner, so working in a field that keeps moving interests and excites her.
After growing up in Malaysia, she came to Australia to study medicine at the University of Western Australia in Perth. Being exposed to lots of haematology rotations piqued her interest in this field.
Then, as a junior doctor, being involved with patients and the malignant facets of haematology, she realised that this was her focus.
Dr Loo felt her personality was suited to haematology and her love for the speciality grew. She moved to Melbourne and started three years of training at the Austin Hospital. One of her bosses there posed a question to her, “why don’t you do the leukaemia fellowship?”.
Dr Loo said she “fell into a fellowship”, which she attributes to serendipity. She was introduced to Prof. Wei, and the following year she started her fellowship at the Alfred, in 2020, which also involved refining all the trial protocols and processes for the AMLM26 INTERCEPT trial.
“The whole AMLM26 INTERCEPT trial idea had been thought of years before I started my fellowship by my supervisor, Prof. Wei,” explains Dr Loo.
“And to do that on a larger scale, in a platform study, would be the most efficient way to assess multiple targeted therapies within one platform.”
Dr Loo has managed a lot of “wonderful patients,” many who have faced life and death situations.
“There is a lot of grace and gratitude that can be learned from patients,” she says.
“Where there’s a deluge of bad things happening to a patient, they tell me that there’s always a lot of other good things that are happening at the same time despite the adverse circumstances.”
Outside the lab and clinic, Dr Loo’s interests are running and music, which are her de-stressors.
She initially learnt to play the piano as a child, then she picked up guitar, and she listens to a range of music to relax – from jazz, classical, pop, and indie rock.
That’s her escape, “because all of us need one, right?”.
* The ALLG AMLM26 INTERCEPT trial strongly aligns with the research priorities of the Leukaemia Foundation’s national research program (novel therapies, new diagnostics, precision medicines, innovative clinical trials), focuses on a blood cancer with high needs, and is a companion precision medicine, genomic-based clinical trial to the Leukaemia Foundation-funded Blood Cancer Genomics Trial. The Leukaemia Foundation provided seed funding to ALLG of $280,000 over two years through the Trials Enabling Program (TEP) partnership, to help establish the project and fund the first 40 patients to enrol on the AMLM26 INTERCEPT trial over the first two years, from October 2021.
* The ALLG is a not-for-profit, collaborative clinical trial group that sponsors, designs, conducts, monitors, and publishes investigator-initiated clinical trials in leukaemia, lymphoma, myeloma, and other blood cancers. The ALLG membership of approximately 450 clinicians is comprised of almost all the haematologists treating blood cancer across Australia and New Zealand. www.allg.org.au
