Trial: Discontinuation of dasatinib

The results of this trial represent an incredible leap forward for CML patients who, like me, are on dasatinib (sprycel). For the patients in this trial, nearly 50% who stopped dasatinib maintained a deep molecular response. The other 50% started taking tablets again and all regained a deep molecular response.

This represents a huge benefit for the patient who could, effectively, remain drug-free but it also represent an economic benefit. What was once considered an expensive drug could soon be considered a drug-for-life for only half of the patients who take it. This could be enough to present a new case to NHS England over funding.

Thanks, Kris

Taken from The Lancet haematology

Summary
Background
First-line imatinib treatment can be successfully discontinued in patients with chronic myeloid leukaemia after deep molecular response has been sustained for at least 2 years. We investigated the safety and efficacy of discontinuing second-line or subsequent dasatinib after at least 1 year of deep molecular response.

Methods
The Dasatinib Discontinuation trial was a prospective multicentre trial done in Japan. Eligible patients taking dasatinib and with confirmed stable deep molecular response were enrolled between April 1, 2011, and March 31, 2012. All patients received dasatinib consolidation therapy for at least 1 year. In those with sustained deep molecular response, dasatinib was discontinued. Patients were followed up every month in year 1 (clinical cutoff), every 3 months in year 2, and every 6 months in year 3 for deep molecular response and immunological profiles. The primary endpoint was the proportion of patients with treatment-free remission at 6 months after discontinuation. Molecular relapse was defined as loss of deep molecular response at any assessment. This study is registered, number UMIN000005130.

Findings
88 patients were enrolled in the consolidation phase, 24 were excluded from the discontinuation phase due to fluctuations in BCR-ABL1 transcript levels. One patient was excluded because of positive expression of major and minor BCR-ABL1 transcripts in chronic myeloid leukaemia cells and the detection of minor BCR-ABL1 transcripts during consolidation. Thus, 63 patients discontinued dasatinib treatment. The 25 patients who were excluded from discontinuation continued to receive dasatinib and none showed disease progression. Median follow-up was 20·0 months (IQR 16·5–24·0). Of the 63 patients who discontinued and were not excluded, 30 patients maintained deep molecular response while 33 patients had molecular relapses, all within the first 7 months after discontinuation. The estimated overall treatment-free remission was 49% (95% CI 36–61) at 6 months. No severe treatment-related toxic effects were seen. Treatment was restarted in the 33 patients with relapse; rapid molecular responses were seen in all 33 patients, of whom 29 (88%) regained deep molecular response within 3 months, as did the remaining four by 6 months.

Interpretation
Dasatinib discontinuation after sustained deep molecular response for more than 1 year is feasible.

Funding
Epidemiological and Clinical Research Information Network (ECRIN).

Visiting Oxford Nanopore Technologies

In April 2015 I visited the Wired Health conference in London, I write the following about a product I saw called the MinION:

Clive G Brown, CTO of Nanopore Technologies, spoke about how his company’s USB stick-sized DNA sequencer will enable an “internet of living things”. He spoke of how he could see consumers using this medical device and having results go to the cloud for diagnosis. Old DNA sequencing machines cost hundreds of thousands of pounds and are huge, this device costs just £650. Clive has a vision for immediate results on a device that can be run anywhere, he used an analogy of building it into a toothbrush so your biology can be sequenced every morning and monitored for changes.

A device like this could be revolutionary in the field of testing epidemics, environmental monitoring and infectious disease control. It’s predictive and preemptive. It could allow general self quantification in the same way diabetes patients track their blood sugar. For any leukaemia patient, like me, who has to have regular blood tests or bone marrow biopsies, several narratives converged for me at this particular moment in time.

Imagine a device that meant we wouldn’t have to visit our consultant regularly but still allowed us to do regular blood tests. It would pick issues up sooner, share results, save the NHS lots of money and do away with bone marrow biopsies. Imagine a device that could track chromosome abnormalities and check immediately for the philadelphia chromosome. The device you see me holding in my hand could be the key to unlocking all of that. This could also be the key to mass screening and therefore the saving of many lives. No pressure there then.

Clive is clearly a man who wants to keep expectations in check but I can’t help but get excited. I spoke to the team during one of the breaks and we are going to talk. This is one to watch!

Last week I was invited to the Nanpore offices in Oxford to give a talk to their staff about self-quantification. The talk ultimately ended up being about the life of a CML patient and the things we go through on a daily basis. It was an emotional rollercoaster and I felt the 150-strong audience were with me every single step. My talks are hard work, I don’t spare any detail but I try and look at things in a light-hearted way. I’m happy to share in order to get people to understand. Understand the patient and the process becomes simple.

After the talk I was given a tour of the offices and laboratories. It’s an incredible organisation with a talented staff who care deeply about their work. It was very humbling to meet so many good people. The CEO, Dr Gordon Sanghera, is driven, intense and inspirational and made me feel very welcome.

This won’t be last you’ll hear from me about Nanopore, I have high hopes from them in 2016. No one ever does something that changes the World because it is easy……they do it to make a difference. I hope I was able to show them enough to see what that difference will make.    Kris Griffin

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A Day In Westminster

I met with parliamentarians yesterday to ask for their support in helping chronic myeloid leukaemia patients access vital, life extending medicines and life insurance. Overall it was a very productive day.

The meetings, held with Mark Tami MP and Lord Avebury, provided an opportunity for me to highlight the fact that patients in England currently are missing out on innovative new drugs whilst patients in Wales have full access. I also explained the difficulties CML patients have getting life insurance cover.

New drugs such as ponatinib (Iclusig®) have the potential to offer patients another treatment option when others have failed and when the only option for many is a stem cell transplant. The system for appraising drugs in England, NICE, says that there are too few patients for them to even consider making ponatinib available on the NHS, they won’t even look at the figures. It doesn’t seem fair that across the border in Wales all patients can be prescribed the drug when here it’s not going to be looked at.

Both parliamentarians were also supportive of my bid to get insurance companies to offer CML patients life insurance, as many of us are being turned down. We’re not asking the insurers to pay out on CML related deaths, but many patients can’t get mortgages without life insurance, so it’s vital that we can be accepted with exclusions for our condition.

There’s plenty of follow up work to be done: letter writing and tabling of parliamentary questions before purdah, the pre-election period in the United Kingdom. I’ll also be meeting up with my local MP Mark Garnier, who has been incredibly supportive over the years, next week to ask for his support on both matters.

Once the dust settles on the general election in May, I’ll be going back down to Westminster to gather more support from MPs and peers. The landscape will be a little calmer by then (I hope) and we’ll put even more pressure on the insurance industry and NICE to give CML patients the access to drugs and services that we deserve. Yesterday was a great start.

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University of York – not helpful

I’ve been highly critical of NICE (National Institute for Health and Care Excellence) in the past but I’ll give credit where it’s due. In this BBC report University of York researchers suggest the Cancer Drugs Fund (CDF) is particularly poor value, diverting money from other patient services. They argue the drugs advice body, NICE, has set its price threshold too high.

Researchers at York say the funding level should be closer to £13,000 to provide the most benefit across the NHS instead of a £20,000 to £30,000 limit that NICE currently work with. Thankfully Sir Andrew Dillon, chief executive of NICE, said: “Unless you think that drug companies will be prepared to lower their prices in an unprecedented way, using a threshold of £13,000 per QALY would mean the NHS closing the door on most new treatments.” I applaud his position on this occasion.

What the researchers at the University of York have failed to take into account is the cost to develop a drug can run to hundreds of millions of pounds and someone has to pay for this. I’m not a defender of pharma and I still believe pharma should do more to make drugs more affordable but this type of scaremongering is unhelpful. We need to work with pharma and not impose dangerous limits on treatment. Readers of this blog will know that the new CML treatments which cost much more than £13,000 per year are, essentially, curing people with Chronic Myeloid Leukaemia. Who knows where these advances will take us, impose limits and we halt progress.

I need to read the report in its entirety but from this overview it appears the conclusions from York aren’t helpful, aren’t clever and don’t take into account the future of cancer treatment. Their recommendations would mean people would die. Perhaps if someone from York is reading this they would get in touch, perhaps we could meet up and perhaps they could tell me just how much my life is worth. I’d also like to ask them what price they put on a cure for cancer and if their report took this into account?

Kris Griffin
Access CML Drugs

BBC Health: NICE ‘sets price too high for NHS medicines’

Ponatinib: Efficacy in patients failing multiple TKIs

I’ve attached a pdf poster that outlines a national study on ponatinib and reports on the efficacy in patients failing multiple TKIs.

The conclusions were:

• Ponatinib has confirmed efficacy in a group of heavily pre-treated patients with CML.
• The probability of achieving cytogenetic response (CCyR) on ponatinib is greater in younger patients, those with prior CCyR and those without early haematological toxicity, confirmed on multivariate analyses (data not shown).
• Event free survival is higher in patients who received fewer TKI prior to treatment with ponatinib.

It makes for interesting study. For reasons of transparency this has been shared with me by an organisation who are working with ARIAD (who manufacture ponatinib).

Thanks, Kris

Download the PDF poster here.

Ponatinib: Wales 1 England 0

After the bad news yesterday, where it was announced that 25 cancer drugs will be removed from the Cancer Drugs Fund (read the full story here), I come with better news. NHS Wales will be providing access to ponatinib for ALL phases of chronic myeloid leukaemia. In England ponatinib is only available on the Cancer Drugs Fund if the patient has the T315i mutation. This progressive step by NHS Wales, based on the Phase 2 PACE trial, gives patients in Wales another, much needed line of treatment against CML. I hope that authorities in England, Scotland and Northern Ireland take note of this step forward when they assess, or reassess, ponatinib for their respective countries.

Thanks, Kris
—

The positive assessment from the AWMSG is the first UK Health Technology Assessment (HTA) of Iclusig

Leatherhead, UK, 9 January 2015 — The Minister for Health and Social Services in Wales has ratified the recommendation from the All Wales Medicines Strategy Group (AWMSG) to approve Iclusig® (ponatinib) as a cost-effective treatment to be used in NHS Wales for the treatment of all phases of chronic myeloid leukaemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL), in accordance with Iclusig’s licensed indication.

CML is a cancer of the white blood cells that is diagnosed in approximately 7,000 patients each year in Europe. The incidence of CML in Wales is 1.4 and 0.9 per 100,000 males and females, respectively. Iclusig is a targeted cancer medicine discovered and developed at ARIAD Pharmaceuticals, Inc.

“We are delighted that the Minister has endorsed the positive AWMSG recommendation, recognising the innovative nature of Iclusig and the potential benefit it can bring to cancer patients in Wales,” said Mark Tanner, General Manager, ARIAD UK. “Our goal is to deliver innovative solutions that address gaps in care for patients who are left with few clinical treatment options. Iclusig offers a new treatment option for many of these patients.”

The approval by the AWMSG was based on results from the pivotal Phase 2 PACE (Ponatinib Ph+ ALL and CML Evaluation) trial in patients with CML or Ph+ ALL who were resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy, or who had the T315I mutation of BCR-ABL. In Europe, Iclusig was approved in July 2013 for the treatment of adult patients with:

• Chronic phase, accelerated phase, or blast phase chronic myeloid leukaemia (CML) who are resistant to dasatinib or nilotinib; who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation;
• Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) who are resistant to dasatinib; who are intolerant to dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation.

“We welcome the ratification of the recommendation from the AWMSG for the treatment of CML and Ph+ ALL with Iclusig in all its licensed indications,” commented David Ryner, Chair of the Chronic Myeloid Leukaemia Support Group. “Although the number of patients qualifying for treatment will be limited, access to Iclusig represents an opportunity to make a significant difference to their lives. We would like to see the same opportunity made available to all other qualifying patients, no matter where they live in the UK.”

About Iclusig® (ponatinib)
Iclusig is a kinase inhibitor. The primary target for Iclusig is BCR-ABL, an abnormal tyrosine kinase that is expressed in chronic myeloid leukemia (CML) and Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Iclusig was designed using ARIAD’s computational and structure-based drug design platform specifically to inhibit the activity of BCR-ABL. Iclusig targets not only native BCR-ABL but also its isoforms that carry mutations that confer resistance to treatment, including the T315I mutation, which has been associated with resistance to other approved TKIs.

About CML and Ph+ ALL
CML is a cancer of the white blood cells that is diagnosed in approximately 7,000 patients each year in Europe.Error: Reference source not found CML is characterised by an excessive and unregulated production of white blood cells by the bone marrow due to a genetic abnormality that produces the BCR-ABL protein. After a chronic phase of production of too many white blood cells, CML typically evolves to the more aggressive phases referred to as accelerated phase and blast crisis. Ph+ ALL is a subtype of acute lymphoblastic leukaemia that carries the Ph+ chromosome that produces BCR-ABL. It has a more aggressive course than CML and is often treated with a combination of chemotherapy and tyrosine kinase inhibitors. The BCR-ABL protein is expressed in both of these diseases.

About ARIAD
ARIAD Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts and Lausanne, Switzerland, is an integrated global oncology company focused on transforming the lives of cancer patients with breakthrough medicines.  ARIAD is working on new medicines to advance the treatment of various forms of chronic and acute leukaemia, lung cancer and other difficult-to-treat cancers.  ARIAD utilises computational and structural approaches to design small-molecule drugs that overcome resistance to existing cancer medicines.  For additional information, visit http://www.ariad.com or follow ARIAD on Twitter (@ARIADPharm).

Iclusig® is a registered trademark of ARIAD Pharmaceuticals, Inc.

You can download the original release here: AWMSG approval_FINAL release_090115

Leukaemia & Lymphoma Research Impact Day 2014

It might seem crazy what I’m about to say
Sunshine she’s here, you can take a break
I’m a hot air balloon that could go to space
With the air, like I don’t care baby by the way

– Happy by Pharrell Williams

There was a definite happy vibe at Leukaemia & Lymphoma Research’s Impact Day yesterday at the Tower Hotel in London. Impact Day is the charity’s annual conference, with a difference. It’s clearly deigned to have an impact on the audience. It did just that! The delegates made up from fundraisers, patients, carers, researchers, Doctors, clinicians, nurses, family members and staff from the charity, were given a blast of progress. What progress! I lost count of the number of times the word ‘cure’ was used. There is a genuine belief that they are the cusp of greatness and whilst looking back at the roots of the charity it truly felt we were standing on the shoulders of giants.

The countless lost to blood cancer over the years has not been in vain, not a bucket rattle wasted and not a clinical trail regretted. We heard about the progress in Childhood Leukaemia (Professor Christine Harrison), Acute Myeloid Leukaemia (Professor Paresh Vyas and Advanced Nurse Practitioner Kirsty Crozier) and Chronic Lymphocytic Leukaemia and Lymphoma (Professor Chris Pepper). Matt Kaizer, Chris West and David Henderson all spoke, with great conviction, about the role of the charity in research, policy and insight respectively. It’s great to see Leukaemia & Lymphoma Research taking policy and insight so seriously, both done well will save lives, albeit in a different way to research; equally important though.

The audience, which was considerably larger than last year, hung on every statistic and anecdote. There were tears and there was admiration. Particular memories for me included the progress in childhood leukaemia where survival rates are now over 90% and the passion in which Kirsty Crozier spoke about her ‘calling’ as a Nurse. It was good to hear Professor Pyas say that the Cancer Drugs Fund has been, “transformational” and Professor Pepper suggest that the best way to make drugs affordable is to create competition in the marketplace. It certainly gives me renewed vigour in hearing that.

A chap called Kris Griffin (!) spoke about patient support and the new online patient services being offered by the charity and Dr Peter Campbell who is Head of Cancer Genetics and Genomics at the Wellcome Sanger Institute gave the audience an insight into individually tailored treatment plans. The progress is more than a little mind-blowing, costs are reducing as is the time taken to sequence; the impact on patient treatment immeasurable.

The day was hosted impeccably by Professor Chris Bunce, whose must surely be a shoo-in to replace Brucie on Strictly, such is his calm, smiling, brilliant demeanour. The day was rounded up perfectly with a closing address by Chief Executive Cathy Gilman who summed up with ease and grace. The hope. The joy. The memory of those that we have lost. The joy that we are step closer to a cure.

“Life is a gift. Use it wisely and live it fiercely.”
– Cathy Gilman

Each loss hurts more now. That we are so close means the pressure is truly on. I can hear buckets being rattled harder, more cakes being baked, running further, cycling harder. To hope. True impact. With heartfelt thanks to everyone, everyday. More happy days.

And all this from a charity who started, quite humbly, in 1960. A seemingly impossible task. This is just the start. Beware cancer, we’re coming for you!

Kris Griffin (middle) with the patient services team and CEO Cathy Gilman from Leukaemia & Lymphoma Research

Cover Stars for Leukaemia Care

Kris Griffin and his family on the cover of the Leukaemia Care magazine.

I’m delighted to be featured on the cover of the latest Journey magazine from Leukaemia Care with Kelly and super-Luca. I’ve written an article inside about my Chronic Myeloid Leukaemia (CML) journey, I hope you enjoy it. You can download the whole magazine here.

I was also thrilled to have been asked along, by Leukaemia Care, last week to a seminar for student nurses at Worcester University. Around 120 student nurses attended and we had a great time. We covered the psychological effects of cancer in what I hope was an accessible way, thanks for listening and for your hospitality. Congratulations to Leukaemia care for organising such an innovative event.   Kris.

http://www.leukaemiacare.org.uk

https://www.facebook.com/LeukaemiaCARE

https://twitter.com/LeukaemiaCAREuk

What is MY PCR survey…

A survey worth spreading…Kris

Dear PCR Campaign Supporters,

As many of you know, 9/22 was World CML Day, the date that symbolically represents the genetic change of Chromosomes 9 and 22 that causes CML. This also marks the one year anniversary of the “What is MY PCR” campaign. In honor of these two events, we are excited to announce the official launch of the PCR Campaign Impact Survey!

Our goal is to gather feedback from you as campaign participants to help us measure our impact and identify areas in which we can strengthen the campaign in 2014. Your voice is critical to shaping this campaign, and we want to hear your feedback! The survey is posted on the campaign website http://www.whatismypcr.org and we encourage you to share this opportunity within your networks as well.

The survey will be open from September 2013 to December 2013. At the conclusion of the survey, we will compile the results into a report in early 2014 to be shared with you and your networks. Currently available in English, Spanish and Thai, we will continue to add translations over the next two months as we receive them from the PCR campaign partners.

We look forward to receiving your feedback. Complete the online survey now!

http://www.surveymonkey.com/s/WhatIsMyPCRImpact

Best wishes for World CML Day,
From PCR Campaign Headquarters

Trial Suggests Imatinib Discontinuation Safe, Some Responses Persist

More positive news on World CML day – we need to keep working towards a cure. K

Trial Suggests Imatinib Discontinuation Safe, Some Responses Persist

Evidence continues to mount that discontinuing imatinib treatment for chronic myeloid leukemia (CML) in the chronic phase is safe. A new phase II Dutch and Belgian study showed only about two-thirds of patients relapsed after discontinuing treatment with imatinib and cytarabine, and all patients remained sensitive to imatinib after relapse.
Tyrosine kinase inhibitors including imatinib have revolutionized CML treatment in recent years, but the need to continue treatment indefinitely is limiting. Several recent studies have begun to suggest that alternate treatment schedules or discontinuation of therapy are feasible among patients with good molecular responses. In a study of the Dutch-Belgian Cooperative Trial for Haemato-Oncology, researchers led by Noortje Thielen, of the VU Medical Center in Amsterdam, 33 patients with a molecular response lasting at least 2 years on imatinib and cytarabine combination therapy were randomized to either continue (18 patients) or cease (15 patients) imatinib treatment. Results were published online ahead of print in July in the European Journal of Cancer.

After a median follow-up period of 36 months, three patients randomized to continue treatment (17%) and 10 patients in the discontinuation arm (67%) had a molecular relapse; all three of the former patients had stopped imatinib treatment after randomization.

The molecular relapse rate at 12 months was 0% in the continued therapy group and 53% in the discontinuation group; at 24 months, those rates were 6% and 67%. In an as-treated analysis (accounting for the patients who ceased treatment in spite of randomization to continue imatinib), the two-year rate was 61% for discontinued therapy and 0% for continued imatinib.
The five patients in the discontinuation group who did not relapse showed a stable molecular response. The 13 patients who relapsed all regained molecular response after a median of 6 months from the restart of imatinib or nilotinib treatment.

“To our knowledge, this is the first randomized trial regarding the discontinuation of imatinib in first chronic phase CML patients who have achieved a durable and stable molecular response,” the authors wrote. “Our results are encouraging.” They noted that the addition of cytarabine to the initial regimen may have contributed to the persistence of response after therapy discontinuation, but that remains unclear.

Further studies on this issue will need to define predictive factors for successful discontinuation of imatinib, as well as of other TKIs including nilotinib and dasatinib, the researchers wrote. “Although imatinib treatment was previously expected to be life-long, our data suggest that, under close PCR monitoring, discontinuation of imatinib is safe in CML patients with a long-lasting molecular response,” they concluded.

http://www.cancernetwork.com/chronic-myeloid-leukemia/content/article/10165/2157668