DNA mapping for cancer patients

Up to 100,000 patients with cancer and rare diseases in England are to have their entire genetic code sequenced.

The Prime Minister will announce £100m has been set aside for the project over the next three to five years.

The aim is to give doctors a better understanding of patients’ genetic make-up, condition and treatment needs, and help develop new cancer treatments.

There are already a handful of targeted treatments – for breast, lung, bowel and blood cancers – where tests for a single gene can reveal whether a patient is likely to respond.

Read the full article on BBC News site here:

http://www.bbc.co.uk/news/health-20663090

Online survey: Improving outcomes for patients with advanced cancer

The Rarer Cancers Foundation is keen to do all it can to support the NHS in ensuring that people with rarer and less common cancers have the best experience of their care and treatment possible.  Collectively we can help to make a real difference to the outcomes for those with advanced cancer.

In order to do this, we need to learn more about the experiences of the people we support around what they value when they have advanced forms of cancer.  The feedback from your charity’s supporters is vital and we would therefore be grateful if you could please circulate the attached letter to your supporters and advertise this survey on your website. The survey can be found here

Your response is really important to us so we can have as broad a picture as possible and therefore we are seeking input from cancer patients, their family members, carers and others who have an insight in this area.

The survey will close on the 30 January 2012 and the findings from this survey and other research that we are currently undertaking for this project will be published late February/early March 2012.

Should you have any queries or need help with this survey please do not hesitate to contact me.

With best wishes

Debbie de Boltz

Executive Director

Rarer Cancers Foundation

incorporating the Rarer Cancers Forum

Mob: 07889 726269

Tel:  01227 738279

www.rarercancers.org.uk

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!