Research Spotlight: Professor John Pimanda

September is Blood Cancer Awareness Month. Here, haematologist Professor John Pimanda talks about myelodysplastic syndrome (MDS) – what it is, how to spot it, and where the research is taking us in the search for a cure.

Extreme fatigue. Bleeding easily. Persistent infections. They’re vague symptoms, easily attributable to a whole range of things – but they can also be a sign of myelodysplastic syndrome (MDS), a cancer of the blood that primarily affects people aged 50 and older.

“MDS is very much like leukaemia, but it’s a more indolent, progressive form, so you tend to deteriorate slowly,” says Professor John Pimanda, head of the Haematological Malignancies stream of the TCRN’s Clinical Improvements into Practice flagship.

“It’s a blood cancer that has a slow progression, and leads to marrow failure and often to leukaemia.”

The only cure for MDS is a bone marrow transplant. However, given the advanced age of many MDS patients, it’s an option that’s available only to a minority of patients. For the rest, there’s azacitidine (AZA), a non-curative drug treatment that can prevent the disease from progressing.

AZA has been registered in Australia for less than 10 years, and despite its status as the only available drug on the PBS for the treatment of MDS, AZA is effective in only 50 per cent of patients. For those who don’t respond to the drug – and for the many who relapse part way through treatment – there are no available options. That’s where Pimanda’s research comes in.

The founder of the NSW Myeloid Malignancy Network, Pimanda is one of Australia’s leading researchers in the field of MDS. He’s played an instrumental role in advancing our understanding of the disease and identifying and progressing treatment options that could extend the lives of many patients.

One of his early achievements was a research study prior to AZA being put on the PBS.

“We got the drug from Celgene, the company who marketed it, for a research study and enrolled 20 patients who didn’t at that time have any treatment options on the PBS,” he says.

“We correlated certain molecular changes in patients’ bone marrow cells to their responsiveness to the drug, and we determined why some patients respond and some patients don’t.”

That research study also revealed the underlying mechanism for drug response, showing that patients whose cells were stuck in the bone marrow environment rather than proliferating were likely to respond poorly to treatment.

In a subsequent study, Pimanda and his team also developed an assay that could be used to identify which patients were likely to respond to AZA treatment.

These insights have paved the way to Pimanda’s current program of work, which continues to progress the research pathway towards better outcomes for MDS patients. Currently,  he’s finishing a study, funded by a TCRN Flagship Support Grant, to modify the aforementioned patient response assay for use in the hospital setting.

Simultaneously, he’s leading a clinical trial to explore the efficacy of AZA in tablet form. The treatment is normally delivered as an injection that’s given daily for a week of every month. Patients usually attend the hospital to receive their injection – a process that, as well as calling on substantial hospital resources, is highly disruptive to patients’ lives.

The new tablet form of AZA could give patients and the health care system a reprieve.

“What we don’t know is whether the tablet is as effective or more effective, what dose patients should have of the drug to show the same sort of efficacy as the injection, so that’s where our research has been focused,” Pimanda says.

Pimanda is leading an investigator-led clinical trial, which is being run through UNSW in partnership with pharmaceutical company Celgene, the manufacturer of the AZA tablet.

“In this trial, patients get the injection drug and then they get the tablet form and we measure how much of the drug has been incorporated into the leukemic cells in each delivery format.”

While AZA has given many patients hope, the fact that it remains ineffective for a large proportion of MDS patients is driving the next stage of Pimanda’s research: identifying novel treatment options to combat the disease.  This could include the use of combination treatments to improve drug response mechanism in AZA non-responders, or the identification of entirely new therapeutic approaches that respond to MDS’s underlying biology.  

It’s a substantial challenge, but this team is ready for it. So are the patients. 

“The research is fun, but we never forget that there’s a patient with expectations at the end of the line,” he says.   

The symptoms of MDS include extreme fatigue, excessive bleeding and persistent infections. If you’re experiencing any of these symptoms, please make an appointment to speak to your GP.