ASH 2011 Conference Highlights

The American Society of Hematology (ASH) is the world’s largest professional society concerned with the causes and treatments of blood disorders. The mission of the Society is to further the understanding, diagnosis, treatment, and prevention of disorders affecting the blood, bone marrow, and the immunologic, haemostatic and vascular systems, by promoting research, clinical care, education, training, and advocacy in haematology. ASH attracts about 20,000 attendees every year (physicians, scientists, laboratory staff, pharmaceutical representatives).  Half of them are international visitors.  There the latest research results are presented and it is an opportunity for attendees to discuss and explain their work.

Dr Austin Kulasekararaj, Haematologist Consultant at King’s College Hospital, London kindly agreed to summarise the highlights of ASH 2011 for us.  He covered progress with existing therapies, promising trial data, new molecular mutations, as well as the revised IPSS (International Prognostic Scoring System).

 

MDS therapies

Combination therapy approaches both in low and high risk MDS was the focus of many presentations, building on the remarkable results obtained with 5-azacitidine and lenalidomide monotherapy.

A multicentre trial using combination therapy of 5-azacitidine (75 mg/m2 subcutaneously on days 1-5) plus lenalidomide (10 mg daily orally for 21 days out of 28 day cycle) in ‘high risk’ MDS patients showed response rate of 72%, with complete response seen in 42% and a median response duration of 16 months. The therapy was well tolerated with minimal toxicities (fever and cardiac) and significantly high response rates.

An interesting study from MD Anderson Cancer Centre assessed combination therapy of 5-azacitidine with vorinostat, a histone deactylase (HDAC) inhibitor in MDS and AML patients who were ineligible for another clinical trial or had liver or renal functions or had poor performance status. This combination was well tolerated in this ‘poor risk group’ of MDS patients with complete response rate of 26%.

Several other combination therapies of were studied in Phase 1 and Phase 2 trials, showing good tolerability and clinical activity

eg Panabinostat (HDAC inhibitor) plus 5-azacitidine,

Belinostat (HDAC inhibitor) and bortezomib (Velcade, proteosomal inhibitor)

Ezatiostat hydrochloride (Telintra) and lenalidomide (Revlimid)

Interestingly, studies using oral 5-azacitidine show good tolerability, with no drug accumulation, and promising clinical responses were observed, although these data are preliminary but the encouraging results show promise for oral azacitidine. A Phase 1 study also evaluated the safety of oral decitabine (Dacogen) in MDS patients and found to have a similar safety profile to intravenous decitabine.

A retrospective pooled analysis of MDS patients treated with lenalidomide (Revlimid) did not show a clear evidence that lenalidomide is associated with an increased risk of secondary cancers (second primary malignancies, SPMs) in lower risk MDS patients and the rate of development of SPMs was what would be expected for this age group when compared with US epidemiological database (SEER database). In another retrospective analysis of RBC transfusion-dependent patients with lower-risk MDS and del 5q, lenalidomide treatment was not associated with a higher risk of AML progression but led to a survival benefit.

Romiplostim (thrombopoietin agonists) showed an improvement in platelet count in one third of low risk MDS patients enrolled in a Phase 2 extension study, but unfortunately the trial was terminated early in view of transient increase in blast count which resolved when the drug was discontinued.

A few other selected studies presented included

• Home administration of 5-azacitidine (Vidaza) in France – showed feasibility, higher level of patient satisfaction and safety of administration. The home administration was not associated with increased side-effects or hospitalisation.
• Romiplostim (thrombopoietin agonists) to increase platelet counts after stem cell transplant.
• Role of azacitidine in Lenalidomide failure in del 5q MDS patients.
• Low dose clofarabine (5 mg/m2 vs. 7.5 mg/m2,dose finding study)-standard dose(D1 to D5) or alternate dosing (D1,D3,D5,D8 and D10), in patients failing 5-azacitidine therapy

The increased understanding of the molecular biology in MDS will help in future development of targeted therapies as the currently available therapies, although clinically effective, do not have a well-defined mechanism of action.

MDS pathogenesis

2011 has been an exciting year with the discovery of new class of molecular mutations in patients with myeloid neoplasms. The discovery of recurrent somatic mutations in RNA splicing factors in patients with MDS, especially in those with ring sideroblasts was highlighted in several presentations including the presidential symposium. Although the functional consequences of the altered splicing factors are being elucidated, this is a major breakthrough in the understanding of the pathogenesis of MDS with ring sideroblasts.

SF3B1 mutations are detected in 80-85% of patients with MDS associated with ring sideroblasts and is also present in 30% of patients with MDS overall. The mutations of the RNA splicing factors are the most common MDS-associated mutations yet to be described and these were detected as a result of whole genome/exome sequencing projects undertaken by several groups. Although SF3B1 mutations conferred a better prognosis, the prognostic impact of the other splicing factor mutations is not clear.

Prognostic models

IPSS-R

Recently, the provisional Revised International Prognostic Scoring System (IPSS-R) has been formulated for assessing the prognosis of primary MDS patients by the International working group for prognosis in MDS (IWG-PM). In this new system, as discussed by Dr.Greenberg in the MDS foundation symposium, cytogenetics remains the key stratification parameter and karyotypic abnormalities are classified into five prognostic subgroups with inclusion of more uncommon cytogenetic subsets. The depth of cytopenias was also considered and the information was obtained from 7012 patients who had not received any disease altering therapy. The IPSS-R divided MDS patients into 5 prognostic groups, with median overall survival of 8.7 years for very low risk group versus 0.8 years for the very high risk group. The value of incorporating of molecular abnormalities into the prognostic scoring systems was also debated and various groups also validated the impact of mutations on different prognostic scoring systems in MDS.

We are definitely achieving a better understanding of the mutations associated with MDS and refining risk model, but it is difficult to know just how any of these might translate into new therapies.

 

We thank Austin for his contribution to our scientific news.

Here is a new article by the Washington University in St. Louis, School of Medicine:

This article deals with the need to develop cancer drugs that target specific gene mutations that develop in MDS.

Introduction: “By mapping the evolution of cancer cells in patients with myelodysplastic syndromes who later died of leukemia, Timothy Graubert, MD, and Matthew Walter, MD, from the Washington University in St. Louis, School of Medicine, have found clues to suggest that targeted cancer drugs should be aimed at mutations that develop early in the disease.”

Read the full article, published 14/03/2012,  here.

A selection of articles from the MDS Beacon highlighting results of recent MDS related research:

• Red Blood Cell-Stimulating Agents May Improve Survival In Higher-Risk MDS Patients Receiving Vidaza 22/03/2012
• Researchers Identify Genetic Mutation Associated With MDS Progression 20/03/2012
• Panobinostat and Vidaza Combination May Be Effective In Higher-Risk MDS Patients (ASH 2011) 6/02/2012
• Lower-Risk MDS Patients May Benefit From Early Stem Cell Transplantation Without T-Cells (ASH 2011) 26/012012
• Home Administration Of Vidaza May Be Feasible For MDS Patients (ASH 2011) 19/01/2012

Update: Response from the writer! (see below)

The BBC1 drama Hunted has featured MDS in one of their story lines – in the most recent episode Polyhedrus.

One of the side characters mentions she suffers from frequent nose bleeds and bruising – and explains it is due to a platelet disorder called MDS.

This is a very brief mention – but we are nevertheless glad to see MDS featured in a mainstream TV programme on a major channel – as it will raise some awareness of the condition.

We are trying to find out from story writer Frank Spotznitz or the BBC why they chose to feature MDS – and would like to congratulate them on having done so.  Do write into the BBC with any comments you may have as patients.

Frank Spotnitz has replied via his TV Blog:
84.At 20:03 14th Nov 2012, Frank Spotnitz wrote:  Thank you so much for all the thoughtful comments. They’re greatly appreciated. We featured MDS because it fit our storyline. I’d be delighted if the episode in some small way helps lead to a broader awareness of the condition.  Http://www.bbc.co.uk/blogs/tv/2012/10/hunted.shtml

 

We also wish BBC had perhaps offered support information after the programme – for anyone affected by MDS.

This is the link to the BBC I player – watch at 7:08 to 8:50 min into the episode:
http://www.bbc.co.uk/iplayer/episode/b01nvm50/Hunted_Polyhedrus/

Many thanks to our 2 patient members who called us to mention this programme.  They were quite surprised!

Please always do let us know if you spot any mention of MDS in the media – as we are not always aware of it.

Following the recent departure of our assistant Alice, MDS UK will be looking for a replacement as soon as possible.  We are looking for someone with strong data analysis skills to work on our patient survey project mainly – as well as to help out in the office with daily tasks.  Good experience dealing with social media tools and websites (preferably WordPress).  This is a varied, interesting and perhaps challenging role, which also does involve contact to patients and families.

We take this opportunity to thank Alice for the time she spent at MDS UK and work she completed and wish her the best in her new role managing data in another charity.

And apologies in advance for any delay in responding to queries and letters – with reduced personnel it will be difficult to answer as promptly as before – thank you for your understanding.  We will let you know as soon as we have found a replacement.

From Monday 15th to Friday 19th October, Channel 4 and Cancer Research UK will showcase TV programmes and fundraising events to raise money for cancer research for Stand Up To Cancer.

Throughout the week, Channel 4 will show documentaries and other programmes supporting those affected by cancer. The week will end with a live fundraising show, aiming to raise millions of pounds.

One of our youngest MDS patients, Daniel Taylor (10 years old) will feature as part of The Big C Choir – a group of cancer patients who have formed a choir, helped by another cancer charity Tenovus.

The choir will feature in a documentary shown on Channel 4 on the 15th October and will also sing live on Channel 4 on Friday 19th October as part of the final fundraising extravaganza.

It’s very impressive work and we encourage everyone to tune in to see Daniel and the rest of the Big C choir!

At this year’s London patient forum meeting, MDS UK committee member Chris Dugmore came up with an ingenious way to raise money at lunchtime for MDS UK, following the theme of marrows.

Chris introduced the competition by saying she had been thinking about how MDS patients have a poorly-functioning bone marrow and would love to have a healthy marrow.  So this was an opportunity for attendees at the patient forum to win one! Supplying one of the organic marrows she and her husband Stephen had lovingly grown in their allotment, green-fingered Chris raised an amazing £75.85 by asking for £1 donations from the generous forum attendees to Guess the Weight of The Marrow.

The lucky winner of the marrow was Fiona Pirilla (also an MDS UK Committee Member!) who came closest to guessing the correct weight of 4 lbs 5 1/4 oz (1,965 g) with a guess of 4.5 lbs.

Fiona took the marrow home and cooked it with pork, onions, tomatoes and cheese.
See below for pictures of Guess the Weight of the Marrow 2012 and the cooked marrow!

Left Chris Dugmore and Sophie Wintrich announce the marrow winner
Right Marrow growers Stephen and Chris Dugmore and Sophie present the marrow to winner Fiona Pirilla
Below The delicious stuffed marrow recipe

To see pictures and the agenda from the patient forum, please click here.

 

 

On Monday 24th September 2012 Kings College Hospital, in conjunction with Celgene UK and MDS UK, hosted the launch of the Life Beyond Limits photographic exhibition. The launch event was well attended by members of the MDS UK committee, press associations, and representatives from King’s College Hospital and Celgene UK.

Life Beyond Limits is a public health initiative which aims to raise awareness of MDS and improve the standards of treatment for older cancer patients. MDS UK is 1 of 8 advocacy groups in the international coalition of charities promoting the Life Beyond Limits campaign.

As part of the campaign, King’s College Hospital will host the exhibition of photographs entitled ‘Facing MDS: When Every Moment Counts’ until 05/09/2012. The photos tell the story of MDS patients from the different countries of the coalition members.

Press Coverage

Press coverage of the launch event and exhibition included an articles in the online healthcare magazines Primary Care Today and Health Matters (available here and here), and event listings in the Telegraph’s photography events guide and in This is London, a what’s-on guide for London (available here and here).

Life Beyond Limits Photo Exhibition Launch

L-R Sam Pearce (General Manager, Celgene UK & Ireland), Prof Ghulam Mufti (Head of Haematology, King’s College Hospital/MDS UK Patron), Prof Rodney Taylor & Sophie Wintrich (Chairman & CE, MDS UK)

L – R Joanne Anderson, Chris Dugmore (MDS UK Committee Members), Prof Ghulam Mufti (Head of Haematology, King’s College Hospital/MDS UK Patron)

L – R Prof Rodney Taylor & Sophie Wintrich (Chairman & CE, MDS UK), Prof Ghulam Mufti (Head of Haematology, King’s College Hospital/MDS UK Patron)

L – R Prof Rodney Taylor & Sophie Wintrich (Chairman & CE, MDS UK), Sam Pearce (General Manager, Celgene UK & Ireland), Judy Woolfenden MBE (MDS patient, featured in the exhibition representing the UK), Prof Ghulam Mufti (Head of Haematology, King’s College Hospital/MDS UK Patron)

L – R Sam Pearce (General Manager, Celgene UK & Ireland), Judy Woolfenden MBE (MDS patient, featured in the exhibition representing the UK)

Public Exhibition in the Ruskin Wing, King’s College Hospital until Friday 5th October 2012

Sophie Wintrich and Alice Murphy of MDS UK Patient Support Group display information materials alongside the photo exhibition at King’s College Hospital.

The Life Beyond Limits initiative aims to raise awareness of Myelodysplastic Syndrome to a wide audience through events such as the photography exhibition.

 

 

 

 

Staff member at King’s looks at the exhibition. The photos show MDS patients from the different countries of the charities behind the Life Beyond Limits campaign.

To the left are images of Judy Woolfenden, an MDS patient in the UK. To the right are pictures of Kirby Stone, an MDS patient from the USA.

 

 

A visitor to King’s looks at pictures of Niels Jensen, an MDS patient from Denmark. To the left, photos of MDS patient Rosmary Pauer from Canada are displayed.

 

 

 

 

 

The exhibition has helped raise awareness of MDS and the MDS UK Patient Support Group. Visitors to the exhibition can take information materials including leaflets and newsletters.

The exhibition has also been used to help launch the first ever MDS World Awareness Day – taking place on Thursday 25th October 2012.