'Your Blood'

An independent supplement distributed by the Guardian on behalf of MediaPlanet who take sole responsibility for its contents.

*Ethnic minorities- why there is a need for more donations

*Blood cancers: Know the signs, push for a diagnosis;

*Haemophilia: Find out about the rare bleeding disorder

See page 10 for CML overview and article.

http://doc.mediaplanet.com/all_projects/11036.pdf

In April 2013 the annual European Group for Blood and Marrow Transplantation (EBMT) conference will be held in London. As part of this conference, there is a dedicated Patient and Family Day on Saturday 6 April where the content is geared towards people who have had a bone marrow transplant – and of course their families.

We would really like to hear two things from you:

1. What topics do you think should be covered in the sessions?
2. Would you be interested in attending the day?

To take part in the Survey go to the Survey page on the left hand lower main menu.

There is a small fee of £10 to attend the day - however, if you answer this survey by 5pm on 21 September you'll be able to attend for free.
Also, as a token of appreciation for your help we will draw three names from the survey respondents and offer a small prize.

More information about the wider EBMT conference can be found here.
www.ebmt.org

Information about how to register for the Patient and Family Day will be available shortly.

With many thanks and kind regards

Jane Apperley
President EBMT Annual Meeting, London 2013
Stem Cell Transplant Programme Director,
Imperial College,
London

Maria H Gilleece
Patient and Family Day Chair
Stem Cell Transplant Programme Director,
Leeds Teaching Hospitals

Richard Davidson
Communications and Marketing

Phase 2 Study of Subcutaneous Omacetaxine Mepesuccinate After TKI Failure in Patients With Chronic-Phase CML With T315I Mutation
Blood. 2012 Aug 15;[Epub Ahead of Print], J Cortes, JH Lipton, D Rea, R Digumarti, C Chuah, N Nanda, AC Benichou, AR Craig, M Michallet, FE Nicolini, H Kantarjian

TAKE-HOME MESSAGE
Results of this phase II trial of 62 patients with T3151-mutated CML who failed previous TKI therapy showed that the protein synthesis inhibitor omacetaxine mepesuccinate potentially offers safe and effective therapy for those with limited options.

Abstract
Chronic myeloid leukemia (CML) patients with the BCR-ABL T315I mutation do not benefit from therapy with currently approved tyrosine kinase inhibitors (TKIs). Omacetaxine mepesuccinate is a protein synthesis inhibitor that has demonstrated activity in cells harboring the T315I mutation. This phase 2 trial assessed the efficacy of omacetaxine in CML patients with T315I and TKI failure. Patients received subcutaneous omacetaxine 1.25 mg/m2 twice daily days 1-14 every 28 days until hematologic response or a maximum of 6 cycles, and then days 1-7 every 28 days as maintenance. Results for patients treated in chronic phase are reported here. Patients (n=62) received a median of 7 (range 1-41) cycles. Complete hematologic response was achieved in 48 patients (77%; 95% lower confidence limit [LCL], 65%); median response duration was 9.1 months. Fourteen patients (23%; 95% LCL, 13%) achieved major cytogenetic response, including complete cytogenetic response in 10 (16%). Median progression free-survival was 7.7 months. Grade 3/4 hematologic toxicity included thrombocytopenia (76%), neutropenia (44%), and anemia (39%) and was typically manageable by dose reduction. Nonhematologic adverse events were mostly grade 1/2 and included infection (42%), diarrhea (40%), and nausea (34%). Omacetaxine may provide a safe and effective treatment for CML patients with T315I mutation. ...read more

With an FDA filing of its wholly owned chronic myelogenous leukemia drug ponatinib under its belt, Ariad Pharmaceuticals Inc.says it will be commercially ready in the U.S. by the end of October and hopes to launch in the first quarter of 2013.
“We want to be ready to go ahead of schedule if the FDA gives us an earlier approval, which we can’t [count] on but certainly we have to be ready for,” CEO Harvey Berger said during an Aug. 2 earnings call.

Ponatinib targets the Bcr-Abl mutation as well as isoforms of the mutation – such as T315I – that cause treatment resistance in CML. Ariad’s development partner MolecularMD Corp. simultaneously submitted a companion diagnostic for the T315I mutation to FDA.
At the agency’s request, Ariad filed a rolling submission in resistant or intolerant CML and Philadelphia chromosome-positive acute lymphoblastic leukemia, the company announced July 30. To complete the application, Ariad plans to submit routine chemistry/manufacturing/control data in the third quarter.

According to the company, 99.9% of the application is complete and the agency will begin a “comprehensive review of the entire file immediately.”
Ariad has requested a six-month priority review for the drug and is requesting accelerated approval based on a single-arm Phase II trial.

The firm does not expect an advisory panel review. “If I had to guess I would say we’re not going to have a panel,” Berger said during the call.
“The data are pretty clear. FDA tends to use panels when there are major questions outstanding.”
And while a user fee date won’t be assigned until the application is complete, Berger stressed during the call that this would not slow down the review.............

The company is planning to launch in Europe in the second half of 2013. Ariad will then need to negotiate coverage and reimbursement in individual countries. Ariad will be starting trials in Japan shortly.

From Relapse To Front-line ...read more

Contrasting Effects of Diclofenac and Ibuprofen on Active Imatinib Uptake Into Leukaemic Cells
Br J Cancer. 2012 May 1;1061772-1778, J Wang, TP Hughes,
CH Kok, VA Saunders, A Frede, K Groot-Obbink, M Osborn,
AA Somogyi, RJ D'Andrea, DL White

TAKE-HOME MESSAGE
ibuprofen should be avoided in combination with imatinib

This analysis of the effects of NSAIDs on uptake of imatinib in CML cell lines determined that leukemic cell response may be influenced by an interaction between certain NSAIDs and imatinib, some with positive impact (diclofenac), others (ibuprofen) negative.

Abstract

Background:
The human organic cation transporter-1 (OCT-1) is the primary active protein for imatinib uptake into target BCR-ABL-positive cells. Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used by chronic myeloid leukaemia (CML) patients on imatinib to manage musculoskeletal complaints.

Methods:
Here we investigated the impact of NSAIDs on functional activity of the OCT-1 (OCT-1 activity; OA) in CML cells.

Results:
Although ten of twelve NSAIDs tested had no significant impact on OA (P>0.05), we observed increased OA (27% increase in K562; 22% increase in KU812 cells, P<0.05) and reduced IC50imatinib when treated with diclofenac. Co-incubation with imatinib and diclofenac resulted in a significantly lower viable cell number compared with imatinib alone. In contrast, ibuprofen led to a significant decrease in OA, an increase in IC50imatinib and thus reduced the cytotoxicity of imatinib. In primary CML samples, diclofenac significantly increased OA, particularly in patients with low OA (<4 ng per 200 000 cells), and significantly decreased IC50imatinib. Ibuprofen induced significant decreases in OA in CML samples and healthy donors.

Conclusion: ...read more

Thanks to Andrew Schorr of Patient Power who produced the following video interview with Brian Druker MD.

Brian Druker: My Vision for CML and the Road to a Cure - http://www.patientpower.info/video/brian-druker-my-vision-for-cml-and-th...

'Results from the ongoing Phase 2 PACE trial of ponatinib reported in June at this year’s annual meeting of the American Society of Clinical Oncology showed that 54 percent of chronic-phase CML patients who were resistant or intolerant to tyrosine kinase inhibitor therapy in the trial, including 70 percent of patients who have a T315I mutation, achieved a major cytogenetic response (MCyR) – the primary endpoint of the PACE trial. Thirty percent of these same patients achieved a major molecular response (MMR). MMR is the primary endpoint of ARIAD’s Phase 3 EPIC trial comparing ponatinib to imatinib that is now underway in newly diagnosed chronic-phase CML patients.

ARIAD’s diagnostic collaborator, MolecularMD Corp., also submitted today a Premarket Approval (PMA) application to the FDA to support commercialization of a companion diagnostic test to identify those CML and Ph+ ALL patients who have the T315I mutation of BCR-ABL.

ARIAD also plans to submit, on schedule, a marketing authorization application (MAA) for ponatinib to the European Medicines Agency (EMA) this quarter'

read full press release here:

http://phx.corporate-ir.net/phoenix.zhtml?c=118422&p=irol-newsArticle&ID...

New Data Confirm Safety of Stopping Imatinib in Leukemia
IMNG Medical Media. 2012 Jun 26, S Freeman

AMSTERDAM (EGMN) - Stopping imatinib in patients who have achieved stable remission of chronic myeloid leukemia for at least 2 years appears to be a safe therapeutic strategy, according to updated results of the Australasian Leukemia and Lymphoma CML-8 trial.

"Approximately 40% of patients who had been in a stable complete molecular response and stopped their treatment are in a complete molecular response with a median follow-up of 3 years," said consultant hematologist Dr. David Ross in an interview at the annual congress of the European Hematology Association.
As of April 2012, 18 of 40 patients remained in stable complete molecular remission (CMR) while off treatment. Although 22 patients had a molecular recurrence at some point after imatinib (Gleevec) withdrawal, they all responded to the reintroduction of imatinib, with most patients rapidly regaining CMR.
These data build on those already released from the STIM (Stop Imatinib) trial (Lancet Oncol. 2010;11:1029-35) and the STOP 2G-TKI study, which have also shown that imatinib, dasatinib (Sprycel), and nilotinib (Tasigna) withdrawal is a feasible therapeutic strategy for some patients with chronic myeloid leukemia (CML).

The CML-8 trial involved 40 adult patients who had been treated with imatinib for at least 3 years and were in CMR for at least 2 years. CMR was defined as no detectable BCR-ABL mRNA as determined by real-time quantitative polymerase chain reaction (RT-PCR) analysis. The latter was checked every month during the first year after imatinib withdrawal, every 2 months in the second year, and then every 3 months for up to 5 years of total follow-up. The last patient entered the trial in 2011, so further data from the trial are likely in the future.
"We've not seen any relapses later than 2 years," said Dr. Ross, of SA Pathology and Flinders Medical Centre in Adelaide, Australia. ...read more

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jul. 27, 2012--
ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced the initiation of the randomized Phase 3 trial of ponatinib, its investigational pan-BCR-ABL inhibitor, in adult patients with newly diagnosed chronic myeloid leukemia (CML). The EPIC (Evaluation of Ponatinib versus Imatinib in Chronic Myeloid Leukemia) trial is designed to provide definitive clinical data to support regulatory approval of ponatinib in treatment-naïve CML patients. The efficacy of ponatinib will be assessed in comparison to imatinib based on evaluation of the primary endpoint of major molecular response (MMR) rate at 12 months. ARIAD expects to complete patient enrollment in the trial by the end of 2013.
“The start of the EPIC trial represents an important milestone in the development of ponatinib in CML and builds on the strong clinical data that we have obtained to date in patients with more advanced disease. We have designed the EPIC trial with comprehensive and well-aligned input from key opinion leaders and regulatory authorities in the United States, Europe and Japan and anticipate strong interest from investigators and their patients,” stated Harvey J. Berger, M.D., chairman and chief executive officer of ARIAD.

http://phx.corporate-ir.net/phoenix.zhtml?c=118422&p=irol-newsArticle&ID...

Leukemia. 2012 Mar 26. doi: 10.1038/leu.2012.85. [Epub ahead of print]
Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML).
Hanfstein B, Müller MC, Hehlmann R, Erben P, Lauseker M, Fabarius A, Schnittger S, Haferlach C, Göhring G, Proetel U, Kolb HJ, Krause SW, Hofmann WK, Schubert J, Einsele H, Dengler J, Hänel M, Falge C, Kanz L, Neubauer A, Kneba M, Stegelmann F, Pfreundschuh M, Waller CF, Branford S, Hughes TP, Spiekermann K, Baerlocher GM, Pfirrmann M, Hasford J, Saußele S, Hochhaus A.
Source
III. Medizinische Universitätsklinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany.

Abstract ...read more