New class of drugs being developed for treatment of polycythaemia vera

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An update on the progress with these newly developed drugs is provided by Associate Professor David Ross, Consultant Haematologist at Royal Adelaide Hospital and Flinders Medical Centre, Adelaide
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Treatment options for polycythaemia vera (PV) are limited at present. Hydroxyurea, a mild chemotherapy tablet, is the most widely used drug treatment in Australia, although the use of interferon is increasing since the recent PBS listing of Pegasys®. Ruxolitinib has shown good results in clinical trials in PV, but in Australia is funded only for the treatment of myelofibrosis.

In 2012 a New York research group reported that the combination of a new drug, ‘nutlin’, with interferon suppressed the growth of PV cells collected from patients.1 They did not treat patients with nutlin, but a related compound being developed by Roche has entered clinical trials as idasanutlin.

Idasanutlin is an inhibitor of MDM2, a protein involved in regulating cell growth and survival. Inhibition of MDM2 has a greater effect on the growth of PV cells than of healthy blood cells. A small Phase 1 clinical trial involving 11 PV patients treated with two different oral doses of idasanutlin was recently published in Blood, one of the leading haematology journals.2 The authors reported improved blood counts, reduction in spleen size, improved symptoms, and a reduction in the level of the JAK2 mutation in the blood.  Preliminary results from the phase 1 trial indicated that the main side effects were diarrhoea and nausea, which were usually mild and occurred in around half of people taking the drug.

A Phase 2 clinical trial of idasanutlin is now recruiting PV patients in whom hydroxyurea has caused intolerable side effects or did not achieve satisfactory disease control.3  This study is open at two Australian sites: the Royal Adelaide Hospital in South Australia and the Peter MacCallum Cancer Centre in Victoria.

Other MDM2 inhibitors are in development, including KRT232 from Kartos Therapeutics. KRT232 is being tested in PV and myelofibrosis internationally, and may become available at some Australian clinical trial sites in the coming months.

References:
1. Lu M et al. Combination treatment in vitro with Nutlin, a small-molecule antagonist of MDM2, and pegylated interferon-2a specifically targets JAK2V617F-positive polycythemia vera cells Blood. 2012;120:3098-3105.
2. Mascarenhas J et al. Oral idasanutlin in patients with polycythemia vera Blood 2019; online June 5 doi: 10.1182/blood.2018893545.
3. Available at: https://www.australianclinicaltrials.gov.au

If you would like to know about the trial, please discuss this trial with your GP or specialist. You can also search for details on the Australian Clinical Trials website by typing idasanutlin into the ‘search for a clinical trial’ category.

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Next Canberra MPN Coffee and Chat – 16 June at 10.30-12

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We have a delightfully supportive and friendly group of MPN patients in the Canberra region so if you live in or around Canberra, please come and join us.
There is always a great deal of news to share, experiences to recount, even sometimes blood test results to discuss!

We are meeting in a lovely warm room at the Peppers Gallery Hotel in new Acton to survive these chilly Canberra mornings and the coffee is excellent.
Our next get together is on Sunday 16 June from 10.30-12.  We hope you can join us.

More details are available HERE

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MPN AA supporting research into a new way to treat iron deficiency symptoms for PV patients

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MPN AA is supporting MPN research at Melbourne’s Peter MacCallum Cancer Centre and Walter & Eliza Hall Institute of Medical Research, investigating a new way to treat iron deficiency symptoms and improve quality of life for people living with polycythaemia vera (PV). 100% of all tax deductable donations to MPN AA from now until the EOFY will go towards this important research.

Please use this link to make a tax deductable donation to this study: https://secure.leukaemiafoundation.org.au/regi…/donate.aspx…

This study is led by haematologists A/Prof Kate Burbury and Dr Sant-Rayn Pasricha, and medical scientist Dr Cavan Bennett.

Here is a lay summary of this study provided by the researchers:

‘Polycythaemia Vera (PV) is a myeloproliferative neoplasm (MPN) in which overproduction of red blood cells leaves patients at risk of complications including blood clots. PV affects ~15,000 Australians. The mainstay of treatment is venesection (blood withdrawal) which removes excess red blood cells and induces iron deficiency (iron is critical for the production of new red blood cells). However, venesection requires insertion of a large needle which can cause discomfort and bruising, is inconvenient as it requires patients to attend a clinic or day centre for care, and can cause fluid shifts which are difficult to manage. Finally, venesection induces total body, rather than blood specific, iron deficiency which can produce adverse effects (such as fatigue, restless legs, and cognitive dysfunction) that impair quality of life.

Iron levels are therefore critical in PV, and are regulated by specific hormones. We believe manipulating iron levels could be used as a protective mechanism to reduce the excessive red blood cell production in PV. Using a series of experimental models, we will uncover the mechanisms of iron regulation specific to PV patients and learn how these can be harnessed to help treat the disease. We will use a novel therapeutic (that is more convenient and predicted to have less side effects than conventional venesection) to manipulate iron levels and study whether this can treat the disease. We expect that the results of our studies will directly lead to a clinical trial for a new class of drug in the treatment of PV.’

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New study: Burden of Myeloproliferative Neoplasms in Australia revealed

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New research led by Cancer Council Queensland and Curtin University has investigated the patterns and trends of myeloproliferative neoplasms (MPN) for the first time in Australia.

The research, published in the American Journal of Hematology, explored the impact of MPN, which affects more than 5000 people in Australia currently, and found that the diagnosis and survival rates of these blood cancers are very similar to those found in recent studies in Europe, the United States and Asia.

Between 2003 and 2014, 8604 Australians were diagnosed with a classic MPN, with a median age of diagnosis of 68 years. About 80% of people diagnosed with MPNs will still be alive five years later.

Co-author Professor Peter Baade, from Cancer Council Queensland’s Viertel Cancer Research Centre, explained that prior to the study there had been no Australian data describing the burden of MPN in Australia.

“Our study adds to a body of data from multiple countries, showing an apparent change in incidence patterns of myeloproliferative neoplasms,” Professor Baade said.

“While the incidence of MPN has been declining since 2003, which is mostly due to a declining incidence of one type of MPN, polycythemia vera, the rates have increased for another subtype,  essential thrombocythemia.

“The reason for these observed trends, particularly the declining diagnosis rate of polycythemia vera, are still unexplained, but may reflect changes in clinical investigation and registry reporting practices rather than a true change in incidence.”

Study co-author John Curtin Distinguished Professor Lin Fritschi, from the School of Public Health at Curtin University, explained that changes in testing for specific genetic mutations may explain some of the trends.

“The specific gene mutations in MPNs have only been identified in the last decade and we now have tests for these genes; this has meant that many of the cases of MPN are diagnosed with blood tests and are not always picked up by the cancer registries,” Professor Fritschi said.

“This change in practice may be responsible for a reduction in reported MPN rates.

“Further research using accurate population-based data, including the collection of genetic information, is needed to assess the impact of changes in clinical practice in Australia.”

The research also involved researchers from University of Adelaide, Queen’s University and Northern Ireland Cancer Registry and Gosford Hospital.

The research paper, ‘Changing incidence of myeloproliferative neoplasms in Australia, 2003-2014’, can also be found online via the American Journal of Hematology: https://onlinelibrary.wiley.com/doi/full/10.1002/ajh.25407.

More detailed information about this research is available from this attachment.  Research findings suppl info

A huge thank you from the MPN AA to all the researchers involved in this study and of course the Queensland Cancer Council and Curtin University.

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MPN Patient Information Afternoon – Sydney – 23 February 2019

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MPN AA and the Leukaemia Foundation collaborated to stage this very successful MPN patient information event at Royal North Shore Hospital in Sydney, attended by 60 patients and family members.
MPN AA is very grateful on behalf of MPN patients for the great job done by Greg Zotos from the Leukaemia Foundation, and also Madeline Thompson on the day.
The presentations were great – firstly Dr Renee Eslick spoke very informatively about “Diagnosis of MPN”. Sue McConaghy, psychologist, spoke on the topic “This is Not the Life I Ordered”, providing ideas about tools we could use to help manage unwelcome and unplanned events in our lives – relevant to all of us at times! We then broke for a lovely afternoon tea, and reconvened to hear Dr Carmel Sullivan speak about how yoga could enhance our physical and mental health and quality of life. Dr Cecily Forsyth followed, and spoke on the topic “Optimal Management of MPN in Australia”, about the latest research on how MPN patients should be managed, going through the 3 main MPN subtypes in order, but acknowledging the shades of grey that exist, and the need to treat each patient as an individual.
Patients seemed to be very engaged, and there was lots of chat in the afternoon tea break, and also some constructive to and fro between patients during the question time.
Videos of the two haematology presentations by Dr Eslick and Dr Forsyth are available for viewing on our MPN Video Presentations page.
Full details of the patient information afternoon, including powerpoint presentations from all the talks are available HERE.
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MPN Patient Information afternoon – Sydney

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SAVE THE DATE. MPN AA has been negotiating with the Leukaemia Foundation and a number of great presenters to hold an MPN Patient information afternoon in Sydney on Saturday 23 February 2019. Further details and opportunity to book a  place coming soon.

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