CML HORIZONS 2014 DAY 3

Late nights and early mornings. A snatched breakfast and sat, politely and on time, for the final session. There’s no rest at CML Horizons, we are straight into STOP trails. Normally spoken in hushed tones by patients, this is closest we get to a cure for CML on TKI therapy. It involves stopping therapy, only with the support of a clinician, once the disease is completely under control.

Giuseppe Saglio took us through the many forms of STOP trials which are mainly undertaken when the patient has achieved a swift (within 24 months) complete molecular response CMR (4 or 4.5 log reduction). There are other factors: women do better and swift progress to CMR is key. Some STOP trials have shown fluctuation below 0.1% of patients who have stopped, but the disease never goes beyond this point – they never lose response. It shows that continual monitoring is a key part to managing this method of treatment. The strength of the TKI the patients takes has a great bearing on the success of stopping treatment, there is a better success rate on nilotinib and dasatinib than on imatinib. Professor Saglio suggested, based on trials, that STOP was not risky and no patient accelerated their condition if the trail did not work. Even multiple stopping strategy can be used, but carful planning undertaken before each try.

Professor Saglio, “discontinuation of drugs will become common clinical practice”.

I’ve highlighted that line, it shows how far we have come and it gives hope for CML patients everywhere.

Susan Saubele provided an overview of interferon therapy in STOP trials. More good news, in particular with people who haven’t received a deep response. One interferon study found only 25% of people lost remission when combined therapy was withdrawn. It appears that major molecular remission (MMR) in interferon therapy is a good place to be; Pegasys interferon therapy achieved a better response. The EURO-SKI trial is the largest and most exciting study currently running, worth watching results as they come in later this year.

Neil Shah presented an individual case study where a woman came off imatinib due to pregnancy in 2001. She didn’t start the therapy again and remains, in 2014, undetectable. She is monitored annually. An amazing circumstance. It’s clear that our understanding of the disease and associated stem cells is growing year-on-year. Results from a variety of different studies look promising. The issue here, for patients, is that the topic is weighed down with scientific content and heavy discussion. I have to take an editorial decision and simply tell you the outlook is very positive. If you want the detailed analysis I would highly recommend Neil Shah’s presentation on the CML Advocates website when Horizons goes live, digitally, shortly after the conference. In the meantime, the morning session brought great hope to the room and there are many people, all over the world, working hard to develop deeper responses for all patients and a TKI cure.

After a smashing book presentation by Mina and Stephene Daban from LMC France, Gail Sperling from The Leukemia & Society in the USA stepped up to present social work and managing distress. I’m a keen believer in mindfulness and I feel it is the area in advocacy where we are most lacking. Whilst clinical treatment is first class, psychological well-being isn’t. Gail spoke about the ‘CML Busters’ – a group set up to deal with information and supporting patients. A very successful initiative. We explored self care and self assessment, ensuring that patients are happy and fulfilled and are dealing with things. The importance of being physically, emotionally, psychologically and spiritually healthy (as much as possible) is key. It’s about finding a balance. I have reservations about the term ‘self’ care – no one should be alone and support is not a solo venture. Gail was reassuring that the focus of her group was ensuring people had people; the ‘buddy’ programme was particularly impressive. The secret to success? Persistence, sharing, staying connected and a sense of humour.

The final session of the conference was from Sarah Liptrott, a clinical research nurse from the European Institute of Oncology in Milan. This fascinating talk on sex, self-esteem and a chronic disease was sincere and interesting. I was particularly impressed by the analysis of side effects in relation to intimacy and sex…kissing with ‘dry mouth’. Very real problems. Fatigue is a key factor and Sarah provided some excellent advice on dealing with it: fluids, setting goals, sleep, routines, eating healthily and yoga. As we heard from Gail, encouraging patients to be proactive in their care helps with self-esteem. In a similar way our treatment is becoming more and more personalised, our care is moving this way too.

I am constantly irritated by studies with tiny (less than 10 respondents) that advocate men staying on treatment whilst trying for a baby. Why take the risk? Sperm bank before treatment starts! There is not enough long-term data that gives us the right to make that decision. This area needs much further discussion, with clear guidelines, supported by stronger data. I feel like I say that every year, perhaps I do.

A wonderful conference. This is the 12th CML Horizons conference and they really go from strength-to-strength, the content will be available digitally on the CML Advocates website in the next 2 weeks and I’d recommend going through the information. Great thanks go out to everyone involved in putting together these marvellous 3 days.

I’d also like to thank Leukaemia & Lymphoma Research (LLR) in the UK for supporting my trip. Victoria Goldsmith, from LLR, accompanied me and I believe the information we bring back and the contacts we made will have a huge impact, not just on CML patients but on ALL blood cancer patients. LLR have been conspicuous by their absence at CML Horizons since I first attended. I applaud the foresight and drive they show in supporting patients via new initiatives like this. Thank you to everyone at Leukaemia & Lymphoma Research, for everything you do.

Time to fly…via Amsteram…wishing everyone a safe journey now and forever.

CML Horizons, Prague 2013 – Day 3

I made it to day 3 despite the best efforts of friends and colleagues trying their best to corrupt and lead me astray. Of course, I resisted on all counts. Last night we were taken around Prague on an old tram and had dinner at a wonderful old venue across town. The half hour walk back to the hotel with team-CML was welcome relief from an intense, exhausting day. It was a good chance, again, to connect with patient group leaders and pharmaceutical representatives to discuss the fish and the flesh.

Omelette for breakfast again, I’m a creature of habit. The conference was soon underway and we were straight into fascinating presentations from Katerina Machova-Polakova and Tim Hughes. I’m not sure what this says about me but it’s certainly a great way to spend a Sunday morning. Better than washing the car and mowing lawns anyway. The topic was monitoring and the advent of much more sensitive techniques. Tim Hughes seemed particularly hopeful about the Cepheid Genexpert machine which requires a tiny blood sample, patients rejoice! It is far more sensitive than the traditional technique. We also touched upon DNA sequencing which can push the boundaries of just how undetectable the patient is. This is going to help us understand just how effective stop trials are and when the best time, if at all, patients can stop treatment safely.

Gianantonio Rosti from Italy spoke in detail about the new ELN guidelines that are being submitted this week. It was heartening to see all 3 common treatments (imatinib, dasatinib, nilotinib) being advocated, the UK should take note. The importance of optimal and sub-optimal responses in a shorter period of time certainly supports the need for the widest range of TKI treatment.

After some useful breakout sessions and a round-up of conference activity it was time to say goodbye over a farewell lunch. Business card swapped, good wishes for the year ahead made and promises to do it all again next year were made. It’s an odd experience to spend an intense 3 days with a large group of people sharing a common vision. We are driven, desperately, to not waste a single minute and to make the most of every opportunity presented.

As I write these closing words on a plane several thousand feet above Frankfurt, Germany, my thoughts wonder to the delegates from 55 countries currently being pinged through the air, like me, back home. The responsibility of the conference weighs heavy, it is now our job to return home and share what we have learnt.

It’s with thanks I sign off; to the scientists, Doctors and nurses, the conference organisers and my buddies Nigel and Tony. To our friends at the conference and all over the world, for those able to support and those in need of support, we are together. For those having a tough time on drugs, recovering from and waiting for a transplant, we are there for you. Nobody said it was going to be easy but we continue to defying gravity every single day.

Thanks for reading.

Kris

CML Horizons Conference, Prague – Day 2

That was a late night! I have a habit of doing this, always the last to leave the party. I won’t tell you what time I crawled into bed, what happens in Prague stays in Prague. So after an omelette, espresso and eye cream the day begins. Upon entering the conference room I’m grabbed by a delegate I met last year who asks me how I am able to look younger than I did last year? Today is going to be a good day!

Jane Apperley, a leading light in haematology and transplant developments from the UK provides an interesting insight into the science of transplants and if they still have a role in treating CML. Of course the answer is yes. It’s clear that TKIs have helped and there is great work still happening, survival rates are good and improving, it’s becoming clear that an early transplant decision presents a better outlook. I look forward to sharing Jane’s slides with blog readers.

Tim Hughes took the stage again to present the latest data on STOP trials. It’s clear that his TWISTER trial is backing up the data on the French trial, 40% of patients stopping imatinib therapy under controlled conditions stay in remission. Where the CML came back treatment resumed and all patients returned to remission. Success criteria improved with combination therapies. Recent STOP 2G-TKI in France have shown that there is a success rate of around 60% with patients on dasatinib and nilotinib who stop under controlled circumstances. There are clearly many STOP trials happening, results are promising, interferon, and possibly immunotherapy, certainly help and it is well worth us keeping our eye on results. It’s important we talk about this and tell people, especially politicians, this is the cure we allude to but worry about pinning our hopes upon. Our hopes are well founded and just in the last year I’ve seen rapid developments.

“Killing the Last Leukeamic Cells” certainly got the attention of the audience and this was a genuine statement. Who’d have thought we would be having this conversation 10-15 years ago? The key, we found out, is detection and a far more sensitive method of tracking but, again, the talk was of cure and absolute belief that this can happen.

I thoroughly enjoyed giving my talk about being connected and using social media as an advocacy tool. It was a very humbling experience to be invited and I’m very grateful to the steering committee for the opportunity. Things went well, I felt like I could have gone on and on, always the same when you are enjoying yourself but I hope delegates were enthused and understood the power of being connected.

The afternoon session covered vital topics like quality of life, adherence and pregnancy. Fabio Efficace presented detailed data on quality of life and the devastating effects of fatigue on the CML patient. Understanding side-effects is key to developing new treatments and managing old ones. Quality of life is something that must go hand-in-hand with staying alive.

On the subject of staying alive we discovered that one fifth of patients surveyed in a recent poll were non-adherent (they didn’t take their tablets when they should). We know that high adherence is key to treatment success so this comes as a surprise. We need to support patients and inform that taking medication every day is important. It is easy to shirk responsibility and hope that someone else manages the message but the reality is that this is collective responsibility and we must all play a part in supporting the CML community and communicating how important adherence is.

Doctor Jane Apperley took to the stage again this time to present CML and pregnancy. There are clearly issues taking TKIs and the advice was for women to come off treatment during pregnancy. For men sperm banking is the safest method. It angers me when I read self confessed experts giving bad advice, particularly about pregnancy. This is not an issue we should be gambling with. Professor Apperley is a leading light on this subject and she is very passionate about enabling patients to become parents. Ultimately there is another life here at stake. I am thankful to my first consultant who ensured I sperm- banked on diagnosis. Without that advice I wouldn’t be a Dad now; thinking about my little boy Luca, this is a very sobering thought.

The day concluded with patient groups and advocates from around the world presenting the work their groups were doing. Bringing developments together in this way certainly gave the day a truly an international feel. It certainly bodes well for International CML Day later in the year.

The evening brings a chance to socialise and relax away from the hotel. What for breakfast tomorrow? What time will I get to bed? And how many more times will I try and crack a joke with a non-English speaker only for it to fall flat?

All these answers and more tomorrow. Same bat-time…same bat-channel.

Kris

CML Horizons 2013 – Day 1 report

After an omelette breakfast and a catch up with some friends we settled down to the first session of the day chaired by the irrepressible Tony Gavin from Leukaemia Care. This European group meeting on Health Technology Assessments (HTA) and cross border healthcare was a healthy start to the day, unlike my breakfast. HTAs and cross border healthcare is a hot topic and lacks clarity and vision, simply bringing the threads together is the challenge, perhaps digital is the answer and both speakers Martin Visnansky and David Ryner alluded to this.

The always impressive Sarunas Narbutas from Lithuania expanded on the issues of cross border healthcare by presenting the key issues and explaining the complex legal technicalities. The structural differences of healthcare systems in each EU country means that there is much work to do before legal implementation on 25th October 2013. After this date we must prepare ourselves for an influx of healthcare visitors to the UK but conversely this opens an opportunity for us to access dasatinib (a drug not readily available in the UK) from another country.

As the main conference got underway we were treated to a video message from the legendary Spanish tenor Jose Carreras, who is a leukaemia survivor. Giora Sharf then provided updates on the inspirational work of the CML Advocates Network.

After a very broad overview from the World Heath Organisation on generic and counterfeit drugs, Jan Geissler took the bull by the horns and presented hard data collated from 55 countries on the availability and occurrence of generic drugs. My concern still remains, are we debating the right issue here? Surely the proliference of generic drugs CAN be a good thing, the pharmaceuticals who developed the drugs would obviously disagree. We should be asking how we ensure standards and quality control the generic drugs. If this leads us to first-class drugs at reduced prices then I don’t have a problem, making sure this happens is the challenge.

The anzovip case study in Serbia presented by Jelena Cugurovic simply highlights the issue of regulation, transparency and quality control. How can a drug be made available to patients when it is not supported by documentation or trial data. This is an opportunity to put pressure on the pharmaceutical industry and drive prices down using the threat of quality generics. It’s clear that this issue needs some very strong guidance and legislation, the organisation in the best position to provide this , the WHO, seem incapable or unwilling. Lives are being put at risk…and I’m tired of writing that.

The final session of the day gave us an update on CML drugs and clinical developments by 3 well respected medical Doctors from Israel, Italy and Australia. We were presented with a number of areas that included the debunking of myths, the efficiency of combination therapy (with Inferferon) and the latest drug efficiency. Doctor Tim Hughes from Australia was particularly impressive with key studies showing how we can predict response rates in the first 3 months of treatment (TIDAL 1 study). The second study (TIDEL 2) showed the importance of switching treatment (from imatinib to nilotinib) after a set period of time if an optimum response isn’t achieved. The survival rate in TIDAL 2 over 4 years is 97%. Time and time again we are seeing that imatinib is a drug that is being superseded by vastly superior 2nd generation drugs. Imatinib has done a wonderful job for us in the past but ultimately we wouldn’t be using it if cost wasn’t an issue.

The day is over; dinner, beer and bed to come. The day has been intense as expected, lots to think about, take home and action. I’m looking forward to tomorrow but I’m going to have to bring my ‘A’ game when I present to over 100 delegates tomorrow. The pressure is on… Have a good evening and thanks for reading.

Kris
PS. I’ll tag the photos when I get home.

Front page of the Independent: Cost of CML Drugs

Well, look here. Front page of The Independent yesterday with “the news” that CML drug prices are way too high. It’s something we’ve known for ages and it’s fantastic that the damaging price of these drugs is being brought to public attention.
I think it is important that we consider the other side of the argument for a moment though, and this is not an attempt to justify the prices and defend the pharmas. These drugs are saving lives and, in some cases, curing a form of cancer. What price on that? These drugs have revolutionised CML treatment and have certainly kept me alive. Do I care about the price? No. I care that they’ve saved my life and it helps that I live in the UK and don’t have to find that money. Do I care that there are people on this planet dying from CML. YES – and this is the issue.   Morally these pharmaceutical companies have an obligation to service each territory to ensure these drugs are available at an affordable price. There are plenty of opportunities to cover research costs but there is bigger picture stuff here…even bigger than the shareholders of these companies. Let’s not use these prices as a stick to beat the industry with, after-all they’ve come up with something truly amazing that is going to change the face of healthcare forever. Instead let’s appeal to their common decency, their moral compass and put the pressure on them to deliver a fair solution. This applies to you too BMS. Your failure to provide a Patient Access Scheme in the England has meant the NHS has not been able to deliver dasatinib as a standard treatment.
What a fantastic opportunity for people to do the right thing. Will it happen? Probably not but I must have faith in the human condition. We can put pressure on the pharmaceuticals,  we can write, ask the awkward questions and make sure they know every time a CML patient dies because they can’t afford the treatment they need. Let’s be brave about this, we thank the industry with all our heart, but the time has come to be bigger than the bottom line.  Kris

The wounded surgeon plies the steel
That questions the distempered part;
Beneath the bleeding hands we feel
The sharp compassion of the healer’s art
Resolving the enigma of the fever chart.
T.S. Eliot (1888-1965) – Four Quartets ‘East Coker’ (1940) pt. 4

The real cancer killer: rip-off prices for drugs set by ‘profiteering’ Big Pharma giants

An influential group of cancer experts has warned that the high prices charged by pharmaceutical companies for cancer drugs are effectively condemning patients to death.

The group of more than 100 leading cancer physicians from around the world, including nine from the UK, accuse the drug industry of “profiteering” – making a profit by unethical methods such as by raising the cost of grain after a natural disaster.

Of the 12 drugs approved by the Food and Drug Administration in the US in 2012, 11 were priced above $100,000 (£65,000) per patient per year. In addition the price of existing drugs of proven effectiveness has been increased by up to threefold.

The specialists say: “What determines a morally justifiable ‘just price’ for a cancer drug? A reasonable drug price  should maintain healthy pharmaceutical industry profits without being viewed as ‘profiteering’. This term [profiteering] may apply to the trend of high drug prices where a life threatening medical condition is the disaster.”

The high prices mean the drugs may not be approved by the National Institute for Clinical Excellence in the UK forcing doctors to fill in a 14 page application apply to the Cancer Drugs fund for British patients who could benefit from them.

In addition, the rising cost of existing drugs in a cash limited health service such as the NHS means treatment is denied to other patients with other conditions.

The authors of the article, published in the journal Blood, are all specialists in blood cancers such as leukaemia, where cancer drugs have proved most effective.

One of the best known – imatinib, whose brand name is Glivec – has proved so successful in chronic myeloid leukaemia that patients who a decade ago survived for a few years can now look forward to a near-normal life expectancy.

But the cost of Glivec has risen from £18,000 per patient per year to around £21,000 in the UK, and from $30,000 to $92,000 in the US. This is despite the fact that all research costs were covered by the original price, and the number of patients treated and the length of time they are on the drug have both vastly increased because of the drug’s success.

Daniel Vasella, former chairman and chief executive of Novartis, the manufacturer, said the original price charged for Glivec in 2001 was considered “high but worthwhile” and was estimated to yield annual revenues of $900 million, enough to cover its development cost in two years. A decade later Its annual revenues in 2012 were $4.7 billion (£3 billion).

The cancer specialists say the revenue earned by Glivec over the last ten years “represent generous profits to the company”. But this has put heavy pressure on those who have to foot the bill. “Grateful patients may have become the financial victims of the treatment success, having to pay the high price annually to stay alive”.

In the US even those with health insurance may pay an average of 20 per cent of drug prices out of pocket. Drug prices are the single most frequent cause of personal bankruptcies in the US.

Three new drugs have been approved for chronic myeloid leukaemia in the last year by the FDA but the prices are “astronomical” the authors say at up to $138,000 a year per patient.

Worldwide only about a quarter of the patients with chronic myeloid leukaemia who could benefit have access to drugs because of the cost. “A small fraction are rich enough to pay individually, and most are treated intermittently or not at all. The effects of these financial pressures on long term survival… are yet unknown.”

In the UK, patients are shielded from the “direct economic anxieties of illness”, the article says.  But Professor Jane Apperley, chair of the Department of Haematology at Imperial College, London, and one of the authors, said high drug prices were still a cause of harm in Britain .

“The price of a drug heavily influences the decision of NICE whether we can prescribe it on the NHS. I am chief of service at Imperial College and we are constantly being asked to reduce our spending. We have to look very carefully at the cost of the drugs we use.”

“Of course we need the pharmaceutical industry to go on developing new drugs. It is very exciting that a number of cancers are now becoming susceptible to these new drugs. But the rising cost is unsustainable. “

“The drugs are very effective at keeping people alive. But if they are priced out of what you can afford you know that you can keep people alive but you can’t afford to do so. It is completely unsustainable for the NHS because the costs are going up every year. We need a serious dialogue about whether we can sustain these costs.”

The authors of the article in Blood conclude: “We believe the unsustainable drug prices may be causing harm to patients. Advocating for lower drug prices is a necessity to save the lives of patients who cannot afford them. We believe drug prices should reflect objective measures of benefit, but should not exceed values that harm our patients and societies.”

The group say they intend to organise regular meetings and campaign for lower cancer drug prices.

A spokesperson for the UK charity Beating Blood Cancers said: “As a charity we want to see an ethical approach to drug pricing . There is no point in us investing in research if the pricing policy means drugs won’t be available to patients.”

In a statement to The Independent, Novartis said: “We recognize that sustainability of health care systems is a complex topic and we welcome the opportunity to be part of the dialogue.  Our critical role, as one of many parties working towards improving cancer care, is to discover and develop innovative treatments.”

“ Novartis innovation in chronic myeloid leukemia (CML) has changed the course of the disease. Before Glivec(imatinib)* and Tasigna (nilotinib), the five-year survival in CML was only 30 percent. Today, nine out of ten patients with CML have a normal lifespan and are leading productive lives.”

“Over the years, our programs have evolved to improve patient access to our medicines. We work together with government health care systems, charities and other payers to build successful cost-sharing models.”

Expert view: ‘Price of drugs is harming patients’

The following is an extract from an article, contributed to by more than 100 leading cancer physicians from around the world, including nine from the UK, published in the journal, Blood.

This perspective reflects the views of a large group of CML experts, who believe the current [high] prices of drugs may compromise access of needy patients to highly effective therapy, and are harmful to the sustainability of our national healthcare systems…

If drug price reflects value, then it should be proportional to the benefit to patients in objective measures, such as survival prolongation, degree of tumour shrinkage, or improved quality of life. For many tumours, drug prices do not reflect these endpoints, since most anti-cancer drugs provide minor survival benefits, if at all.

As physicians, we… believe the unsustainable drug prices in CML and cancer may be causing harm to patients. Advocating for lower drug prices is a necessity to save the lives of patients who cannot afford them … For CML, and for other cancers, we believe drug prices should reflect objective measures of benefit, but should also not exceed values that harm our patients and societies.”

An ethical price tag? Cancer drugs

Brands used for the treatment of chronic myeloid leukaemia

Imatinib (Glivec) £21,000 per patient per year – Novartis
Designed from first principles, it proved hugely effective and unexpectedly turned into a blockbuster, earning billions of pounds for its makers.

Nilotinib (Tasigna) £21,000 – Novartis
Designed for patients who fail to respond to Glivec, Novartis reduced the cost to get it past Nice, whilst increasing the cost of Glivec.

Dasatinib (Sprycel) £31,000 – Bristol Myers Squibb
Also designed for patients who cannot take Glivec. But it has not been approved by Nice for use on the NHS because of its high cost.

Bosutinib (Bosulif) £76,000 – Pfizer
For patients who suffer side-effects from the other drugs. It won approval in the US in 2012 but is awaiting a licence in the UK.

Omacetaxine (Synribo) £100,000 – Teva
For patients who cannot tolerate other drugs. Approved in US in 2012 but awaiting licence in the UK.

Ponatinib (Iclusig) £90,000 – Ariad
A third-generation drug which works in a different way. Approved in the US in 2012 but awaiting a licence in the UK.

JEREMY LAURANCE    MONDAY 29 APRIL 2013

http://www.independent.co.uk/news/uk/home-news/the-real-cancer-killer-ripoff-prices-for-drugs-set-by-profiteering-big-pharma-giants-8591825.html

TKI survey on behalf of CML Advocates Network

A request from the CML Advocates Network who I fully endorse and would ask you complete the survey. Many thanks, Kris

—-

Imatinib, dasatinib and nilotinib are a tyrosine kinase inhibitors (TKIs) that have been established as effective therapies in chronic myeloid leukemia. While imatinib (marketed as Gleevec/Glivec), and in some markets nilotinib (marketed as Tasigna) as well as Dasatinib (marketed as Sprycel), have been available for some years, non-original copy versions of these drugs have also been provided to CML patients in a number of countries. With the patent ending on Glivec/Gleevec from 2013 in some markets, the use of generic TKIs in CML is becoming more and more widespread.

With the CML Horizons 2013 patient conference putting a spotlight on the situation of generics and copies in CML therapy, this survey intends to understand the availability of original TKIs and other non-original TKIs for the treatment in CML in countries all across the globe. It also aims to understand how CML patient groups are addressing the issue of quality assurance when generics and copies become available.

This survey is run by the CML Advocates Network without any commercial interest and without support from any pharmaceutical company. The results of this survey will be presented to the community at the CML Horizons 2013 meeting in May.

It should take 10-15 minutes of your time to complete the 10 questions. We would like to cover as many countries as possible – your contribution is greatly appreciated and will help us a lot!

Please respond to the survey here: http://www.cmladvocates.net/tkisurvey
(and please also respond if NO generics/copies are available in your country, which is equally important to know)

Can you please respond latest by 12 April 2013?

Many thanks and best wishes,

Jan (on behalf of the CML Advocates Network)

Report: deaths from Chronic Myeloid Leukaemia (CML) have halved

The National Cancer Intelligence Network (NCIN) have this week released a report which has shown that deaths from Chronic Myeloid Leukaemia have halved since TKIs were introduced in 2001.
The report states that “What’s even more promising is that, in the last four years, second and third generations of these drugs have been developed. We believe more and more CML patients have been receiving TKI’s and we’d predict that the improvements in survival should be even greater in the future” – However, we know of the challenges patients will face on long term access to dasatinib, especially with no firm long term commitment to the future of the CDF. If we take into account the success of these new drugs over the last 4 years I predict that survival figure will sky-rocket. More reason to ensure access to all of the drugs for everyone.
Kris

IMPROVED TREATMENTS FOR CHRONIC MYELOID LEUKAEMIA HAVE DRAMATICALLY INCREASED SURVIVAL

Survival for people diagnosed with Chronic Myeloid Leukaemia (CML) has risen by nearly half, with around 58 per cent of people surviving their disease for at least five years compared with only around 40 per cent in the late 1990s, according to a new report from the National Cancer Intelligence Network (NCIN), published today (Wednesday)*.

The improvements are largely down to a family of drugs called Tyrosine Kinase Inhibitors (TKIs) which have now become the standard treatment for the disease. The first of these was imatinib (Glivec), which was licensed in 2001.

The Northern and Yorkshire Cancer Registry and Information Service (NYCRIS), on behalf of the NCIN Haematology Site Specific Clinical Reference Group (SSCRG), looked at the rates of people in England getting, dying from and surviving a range of different blood cancers between 1995 and 2008. And it is the first national study in England to look at survival for different types of leukaemia.

For patients diagnosed with CML, researchers found that the chance of surviving the disease for at least five years after diagnosis rose from 41 per cent to 57 per cent in men and from 38 per cent to 59 per cent in women between the late 1990s and the early 2000s**.

CML is a relatively rare form of leukaemia*** that mostly affects older people, with around 700 cases diagnosed in the UK every year****.

Dr Robin Ireland, chair of the SSCRG at the NCIN, said: “It’s really exciting to see the enormous difference new drugs can make in treating cancer. And, as this new data shows, TKI’s can be considered a revolutionary treatment for Chronic Myeloid Leukaemia.”

“Basic research has given us a greater biological understanding of cancer tumours, which has led to the development of successful targeted cancer drugs that are now the first line treatment for CML. TKIs target cancer cells by blocking the molecules they make, which stops them from multiplying. These drugs have completely changed the outlook for patients with this disease and it’s the first example of our improved understanding of cell molecular biology leading to the design of a specific inhibitor of the disease.

”Dr Steven Oliver, Haematological Cancer Epidemiology Lead at NYCRIS and lead author of the report, said: “This report shows that, although the number of people developing Chronic Myeloid Leukaemia hasn’t changed much since 2001, survival from the disease has greatly improved.”

“What’s even more promising is that, in the last four years, second and third generations of these drugs have been developed. We believe more and more CML patients have been receiving TKI’s and we’d predict that the improvements in survival should be even greater in the future.”

“Chris Carrigan, head of the National Cancer Intelligence Network (NCIN), said: “Being able to link data on the diagnosis, treatment and outcomes for cancer patients allows us to identify where improved cancer care is having an effect on peoples lives. The improvements in survival demonstrated here highlight the difference that effective treatments can make.”

Notes

*Haematological Malignancies in England: cancers diagnosed 2001 – 2008.Note that analyses of deaths from blood cancers for 2001-2008 were also reported, along with 5-year survival figures for patients diagnosed with different blood cancers in 1995-1999 compared with those diagnosed in 2000-2003.

**Absolute change in CML 5-year survival rates, in England, 1995-1999 compared with 2000-2003. Male rates 40.7% and 56.9%; female rates 38.4% and 58.7%, in 1995-1999 and 2000-2003 respectively.

***Leukaemias are a group of malignant diseases that affect the production of white blood cells – the body’s guards against foreign cells and infections. The different types of leukaemia affect different organs and vary in how quickly they spread. Different types of leukaemia affect different age groups and there are some wide differences in survival found across the age groups in certain forms of the disease.

**** There were 710 cases of CML registered in 2010 in the UK (Cancer Research UK Statistical Information Team)The NICE guidance recommends standard-dose imatinib as the first-line treatment for CML.

Source: http://www.ncin.org.uk/news_and_events/improved_treatments_for_chronic_myeloid_leukaemia_have_dramatically_increased_survival.aspx

Imatinib – the dawn of targeted treatments

An excellent piece from the Cancer Research UK Science Blog:

Thirty years ago, we published research that was a key early step in the journey towards the first genetically tailored cancer drug, imatinib (also known as Glivec, or Gleevec in the United States). This drug changed the landscape, not just for those for whom it was designed – people with chronic myeloid leukaemia – but for cancer treatment as a whole.

Imatinib is unlike the conventional chemotherapy drugs that came before it. Such ‘cytotoxic’ chemo indiscriminately kills rapidly dividing cells. These include the intended target – cancer cells – but also some healthy cells like those lining the gut and mouth and hair follicle cells. Imatinib on the other hand, is specific to a molecule produced by certain cancer cells.

Imatinib featured on the front cover of Time magazine and was hailed as a “magic bullet”. It was indeed a revolution of its time – after it was approved in 2001, bed-ridden patients who’d been given just months to live were up on their feet and re-energised, thanks to their cancer being eradicated by imatinib. The story of imatinib – outlined in more detail below – is proof that if you understand the precise abnormality that is driving the cancer, there is hope for a cure. And we are proud that our early laboratory work provided a crucial stepping stone on the road to its development.

Early work
In the early 1980s, in the lab of our then Director General Sir Walter Bodmer, Cancer Research UK scientists were hard at work examining the DNA in cells. Imatinib was yet to be dreamt up, but these scientists were carrying out crucial early lab research that would increase our understanding of the genetic causes of chronic myeloid leukaemia and lay the foundations for this remarkable drug. Nigel Spurr, Peter Goodfellow, Ellen Solomon and Walter Bodmer from the charity were working with colleagues from the National Cancer Institute in America and Galton Laboratories. They discovered that the ABL cancer gene was located on chromosome 9.

On the surface, this may not be the most exciting-sounding finding. But at the time, it was like finding a needle in the proverbial haystack – it was already known that nearly all (95 per cent) people with chronic myeloid leukaemia had a major fault in this chromosome. In these people, part of chromosome 9 breaks off and sticks to chromosome 22, forming what is known as the Philadelphia chromosome – a major discovery made a decade earlier by Janet Rowley at the University of Chicago. Our scientists’ work opened up the question – was the newly located ABL cancer gene involved in this crucial disease-causing rearrangement?

A few months later, Cancer Research UK-funded scientist Nigel Spurr was part of the Dutch and American collaboration that answered the question. They demonstrated that this was indeed the case. The ABL cancer gene was definitely involved – it broke off from chromosome 9 and joined with part of chromosome 22.

A few years later, in 1985, the gene to which ABL joins on chromosome 22 was identified as BCR. And after further research, it became clear that it was the ABL-BCR ‘fusion gene’ that was fuelling the cancer – by making the cell produce a molecule (called a tyrosine kinase) that encourages white blood cells to incessantly grow and multiply.

Finding a drug
With the crucial molecular players identified, the hunt was on to find a drug that could stop them. Biochemist Nicholas Lyndon then working for Ciba-Geigy (now Novartis) and Brian Druker who was training to be a cancer doctor at the Dana-Farber Institute in America, were inspired by the prospect. They had realised that if you could block ABL-BCR, you could potentially stop CML in its tracks.

Lyndon and his team set about screening hundreds of chemicals to come up with a drug that would block the tyrosine kinase. Together with Brian Druker, he tested some likely candidates on cells grown in the lab and hit upon one that worked – they tweaked it to develop imatinib.

Astonishing results
The drug worked in cells and mice, but would it work in patients? In the mid-1990s, Brian Druker led the team which carried out the clinical trials. The results were nothing short of astonishing. The drug worked quickly and effectively in patients for whom there had previously been no hope, and imatinib became the fastest drug to be approved in history.

Before imatinib, the only real option for CML patients had been debilitating treatment with interferon or a stem cell transplant. Now, the patients could take a tablet, once a day in the comfort of their own home, and there was no need to go to hospital for treatment. And because the drug was so targeted, the side effects were limited. As Brian Druker who led the trials sums it up, “In short, it is a simple, effective treatment that disables the cancer without disabling the patient.”

It is no surprise, then that in 2009, Lyndon, Druker and another colleague Charles Sawyers, were awarded the Lasker–DeBaker Clinical Medical Research Award for “converting a fatal cancer into a manageable condition”. And earlier this year, Druker, Lyndon and Rowley were given yet another prestigious award: the Japan Prize for their part in “the “development of a new therapeutic drug targeting cancer-specific molecules”.

What about other cancers?
Encouraged by the success imatinib had seen in treating CML patients, scientists then started to turn their attention elsewhere. Could imatinib produce a similar miracle effect in other cancers where tyrosine kinases were overproduced?

In 1998, some Japanese scientists found a possible candidate – gastrointestinal stromal tumours. These tumours develop from the cells of the connective tissues that support the organs of the digestive system – the gastrointestinal tract – and generally don’t respond well to chemotherapy or radiotherapy. They found that gastrointestinal stromal tumours may be caused by faulty KIT genes. And faulty KIT genes were already known to make the cell overproduce tyrosine kinase – which meant that imatinib could work in these patients. Soon, international trials were underway to test whether imatinib could indeed be used to treat gastrointestinal stromal tumours.

From lab to clinic
Having been involved in very early lab work twenty years earlier that had led to imatinib’s development, we were then involved at the other end of the spectrum – helping to test the drug in clinical trials for people with gastrointestinal stromal tumours. Professor Ian Judson led these early trials at the Cancer Research UK Centre for Cancer Therapeutics at the ICR, in collaboration with EORTC Soft Tissue and Bone Sarcoma Group.

It was this important work that led to imatinib being approved to treat people with advanced gastrointestinal stromal tumours. Today, a sample of a patient’s tumour needs to be tested first to see if it has a faulty KIT gene before they are prescribed imatinib.

And that’s just the beginning…
Imatinib set the stage for tailored cancer treatments. Today, there are many more targeted cancer therapies in use or in trials, several of which are underpinned by our work – erlotinib (Tarceva), gefitinib (Iressa), cetuximab (Erbitux), trastuzumab (Herceptin) and vismodegib (Erivedge), to name but a few.

Our part in the story of imatinib was small but significant, and something that we’re tremendously proud of. Nobody could have known at the time how far-reaching the consequences of our research on the ABL gene would be, but that is the way of laboratory science. We don’t always know where our research today will lead, but we do know that funding work to unravel the inner workings of cancer is crucial to find the cures of tomorrow.

Around 40 per cent of our research is on fundamental biology, and there are countless examples of biological insights in the lab that have laid the foundations for new cancer treatments. Where will discoveries made in our labs today lead to in the future? Time will tell, but there’s no doubt that more ingenious ways to beat cancer are around the corner.

by Josephine Querido

http://scienceblog.cancerresearchuk.org/2012/10/25/imatinib-the-dawn-of-targeted-treatments/

CML Survey – please take part

As many of you may already know, the link between non adherence (previously referred to as non-compliance – that is forgetting to take or deliberately not taking oral medications as prescribed) to tyrosine kinase inhibitors (TKIs) and poor outcome or lose of response, has been proven in two big research studies one by the Hammersmith hospital London and the other Adagio study – Universitair Ziekenhuis (UZ) Gent, Gent, Belgium.

The Leukaemia Patients Advocates Foundation, and CML advocates network has now launched phase 2 of its International CML Adherence Survey. The survey will be available in 12 languages, The goal of this survey, which builds on a pilot survey that had already revealed invaluable insights, is to better understand patients’ attitudes to taking their oral medication for the treatment of CML. It aims to gain greater understanding of patient attitudes and behaviours surrounding adherence, and ultimately help support physicians and patients to improve compliance and to develop adherence tools.

The survey, which is completely anonymous, is available via this link, www.survey.euro.confirmit.com/wix/p929997428.aspx.  They want as many CML patients as possible to fill it in so they can identify differences between countries in adherence levels and attitudes and improve compliance and to develop adherence tools that may be country specific.

Anonymity and confidentiality of all responses will be assured, so results cannot be attributed to any individual patient. Participants in the survey need to be CML patients that are currently under TKI treatment and be at least 18 years old.

Please help with this very valuable project, and fill it in as honestly as you can.  The results will be published in peer reviewed journals, and will help guide physicians in the future treatment of all CML patients.

Thanks,

Kris

National Virtual CML Patient Summit – 9/22/12 – CML Awareness Day (US)

Basketball player Kareem Abdul-Jabbar is an NBA legend and it was only recently I discovered he has had CML since December 2008. He takes Glivec and has been in remission since February 2011. He is now a spokesperson for Novartis, the company who developed Glivec

As part of CML Awareness Day Kareem is one of the speakers at the free National Virtual CML Patient Summit in the US.

They have put together an outstanding panel and if you get an opportunity to view the six sessions then I urge you to do so. Details follow.

Thanks,

Kris

National Virtual CML Patient Summit – 9/22/12 – CML Awareness Day
Living Well with CML: A Virtual Patient Summit
Time: 1:00 pm – 6.30 pm EST/ 10:00 am – 3:30 pm PST
Cost: Free
Presented by: The National CML Society and a panel of CML experts with special guest CML patient and advocate Kareem Abdul-Jabbar
Sponsored by: Novartis Oncology

This unique online educational program will be live-streamed from New York directly to individuals in the United States who are impacted by Chronic Myelogenous Leukemia (CML). During the live event, notable professionals will provide information about survivorship, health and living well with this blood cancer.

Viewers will be able to submit questions during the webcast and get answers on the spot. The highly interactive program will also include in-studio cooking during nutrition discussions as well as exercise demonstrations.

Participants include Greg Stephens, Executive Director of the National CML Society and patient advocate Kareem Abdul-Jabbar, who was diagnosed with CML in 2009. The six sessions will also include healthcare professionals with expertise in CML and cancer support.
www.cmlpatientsummit.com