ASH 2011 Advocacy Report on CML

Written by Victoria Louise Crump-Haill – Digital Strategist/Account Director‏

 

Every year in December, about 21,000 haematologists and health professionals  – as well as a small number of patient advocates – met at the Annual Meeting of the American Society of Haematology (ASH) in San Diego to learn about latest news from research in leukemias, lymphomas and other blood disorders. We have attended the scientific Chronic Myeloid Leukemia (CML) sessions at ASH 2011 and are summarising the most important presentations and posters, complemented by a patients’ perspective and an overview of patient advocacy activities at ASH.

CML Education Session

Traditionally, the first day of the ASH Congress features Education Sessions. These sessions provide haematologists with the overall picture on a specific disease, including its biology, standard of care, current therapeutic challenges, results from recent trials and future outlook. This year, Prof Neil Shah (USA), Andreas Hochhaus (Germany) and Junia Melo (Australia) presented the state of play in CML treatment and care.

Great success in CML – but not for all patients: Dr Neil Shah opened the session highlighting the 8 year results of the IRIS study, with only 7% of CML patients dying from CML within 8 years when treated with Imatinib as a first-line therapy. Life expectancy is close to that of the healthy population. Serious side effects of oral CML therapies are relatively rare and decreased in incidence within the first two years of therapy. However, about one third of newly diagnosed CML patients required alternate CML therapies due to no response, resistance or intolerance. Shah highlighted the importance of the milestones for suboptimal response and treatment failure defined in the ELN treatment recommendations.

To optimise response, the French SPIRIT study demonstrated that adding low-dosed pegylated Interferon to Imatinib might be beneficial. Looking at second generation drugs (Dasatinib, Nilotinib) in first line treatment, it was clearly demonstrated that progression rates into advanced disease were much lower on Nilotinib and Dasatinib than on Imatinib, while tolerability was comparable. However the Billion Dollar question remains unanswered whether the second generation CML drugs should be administered first-line. While efficacy is clearly superior to Imatinib, side effect issues and higher treatment costs require further consideration. Dr. Andreas Hochhaus (Germany) outlined that due to the successes of CML therapy, 250,000 Europeans will be alive by 2050 that have, or have had, CML, which brings challenges to healthcare budgets. Further trials will clarify the issues of optimisation of CML therapy, which might bring three phases – intensive induction, response consolidation and then potentially therapy discontinuation. Patients are highly encouraged to continue participating in trials.

To support that, Junia V Melo (Australia) highlighted that “operational cure”, with CML being under control while on continuous therapy, can only be seen as a partial success. Melo highlighted that a recent study had revealed that almost all “PCR undetectable patients” were still positive using the more sensitive DNA-based PCR, raising the question that “complete molecular response” may have been a failed promise. In addition, quality of life and treatment costs were major issues in long-term chronic management of CML with continuous therapy. Looking at stem cell transplant, the only curative treatment for CML today, Melo mentioned that even though it may cure, it is a “big price to pay” for many of the survivors, with chronic Graft-versus-Host-Diseases having a major impact on their quality of life.

For that reason, transplant does only play a minor role in CML treatment today, making up only 3% of transplantations, demonstrating the success of current oral therapies. However, Hochhaus outlined that transplantations in high risk CML patients were generally done too late today. He raised that in lower income countries, transplant costs might also be lower than life-long TKI therapy.

As a about half of patients in TKI-induced absence of residual disease have shown not to relapse after stopping therapy, discontinuation studies are a hot topic in CML in 2011. Melo outlined the results of the French STIM stop study where 41% of Imatinib patients in complete molecular response did not relapse within 18 months after cessation of all therapy. Another French study presented by Delphine Rea (France) outlined that relapse rates might be lower on second generation CML drugs. Prognostic factors which patients relapse after cessation and which don’t are still unclear though.

Stopping therapies after TKI treatment might be an option for a minority of CML patients. For all other patients, new drugs or immunological approaches are needed to selectively target the leukemic stem cell, as well as new diagnostic measures to monitor the effect of those treatments. Melo highlighted four strategies on targeting stem cells are currently addressed by researchers with new drugs: Inhibit self-renewal of stem cells, reverse the dormancy of stem cells to make them susceptible to TKI therapy, induce differentiation of stem cells, or induce cell death.

In terms of adherence to CML therapies, Hochhaus highlighted the results of the global patient network CML Advocates Network adherence study, where about one fifth of CML patients admitted to miss doses, and 7 out of 8 stated forgetfulness as the reason. With regards to tools to improve adherence, he stressed that patients don’t want to be reminded every day that they have CML. Hochhaus highlighted that the CML community is an outstanding example in patient advocacy, not to be seen in many other cancers, which has become a credible partner of clinicians and industry, as well as an independent political voice on access to diagnostics and therapy, reimbursement and information to patients.

CML Patients’ perspective on the Clinical  Sessions on CML

“Can we aim at a cure?” This was probably the leading question lingering behind many presentations at ASH this year. The question was first expressed by Junia V Melo (Australia) in the Education Session on CML, but also in many other presentations and posters discussing ‘operational’ vs ‘real’ cure, therapy optimisation to increase complete molecular response rates, discontinuation studies, new mechanisms to target stem cells, and improvement of diagnostics to detect minimal residual disease on a very low molecular level.

The performance of the approved CML therapies continues to improve over time. Giuseppe Saglio presented the 3 year follow-up data of the ENESTnd study that compared Nilotinib with Imatinib as a first-line treatment. Compared to the 24 month data presented at ASH, there have been no surprises – which are good news for patients: no increase in liver events, no patient discontinued due to blood sugar levels, no worrying cardiac issues observed. The 3 years follow-up demonstrates that Nilotinib is clearly superior to Imatinib for treating newly diagnosed CML patients, with faster and higher response rates across all risk groups, and a significantly lower risk of progression, and connected to that, lower risk of death. To assess whether dose escalation of Nilotinib to 2x400mg, or a switch from Imatinib to Nilotinib 2x400mg, is an option for those that responded on ENESTnd suboptimally or failed therapy, Dr Andreas Hochhaus presented the ENESTnd extension study where slow responders could receive a higher dose of Nilotinib, or switch to Nilotinib if in the Imatinib arm. The switch was beneficial for a majority, so dose optimization has shown to be safe and increases responses.

Unfortunately no 30 month update of the DASISION study comparing Dasatinib and Imatinib in first line was presented at ASH 2011 (while at EHA 2011, both 24 month data of Nilotinib and Dasatinib was presented, allowing a comparison of both new 2nd generation drugs).

Dr. Jorge Cortes presented the 24 month follow-up data of the BELA trial with Bosutinib, another second generation TKI that is highly selective on BCR-ABL, being active against Dasatinib- and Nilotinib-resistant mutations except T315I and V299L. While the primary endpoint of the trial was not reached as complete cytogenetic responses were not shown to be different between Bosutinib and Imatinib, molecular response rates were significantly superior. Bosutinib may offer a new therapeutic option for patients with newly diagnosed CML, and was submitted for marketing approval in Europe and USA.

An update of the French SPIRIT trial combining Imatinib and pegylated Interferon, after dose optimization of Interferon which improved tolerability largely, suggested that the Imatinib-PegIFN combination is clearly superior to Imatinib alone, significantly improving response rates.

Dr. François-Xavier Mahon (France) presented an update on the French Imatinib discontinuation study “STIM”. 61% of patients lost their molecular response within 22 months. Dr Mahon clearly stated that he would recommend discontinuation only within a clinical trial with close molecular monitoring. Taking into account the number of months without treatment in the study, Dr Mahon added that the savings within the STIM trial for the French healthcare system alone were estimated at 4 million Euros.

Exciting news were presented on Ponatinib (AP24534) as well as early data on DCC-2036. Both drugs have the capabilities of targeting T315I, which may be the “last bastion” in chronic phase CML. With Imatinib, Dasatinib and Nilotinib as approved therapies, Bosutinib striving for market authorisation, Ponatinib demonstrating very convincing data even way beyond T315I, we’re moving towards a situation not dreamt of just 10 years ago: With CML patients having an equivalent risk of dying from CML than dying from any other cause and, and with a series of highly effective drugs available for battling any kind of nasty mutation – if CML is diagnosed early. Important research findings on quality of life data, data on co-morbidities like diabetes, and the special challenges of elderly patients have been presented as well – which is important for patients facing life-long treatment of a chronic disease.

Unfortunately, there is little progress on the front of advanced phase and blast phase CML. A rough estimate of 90% of all presentations at ASH 2011 addressed only chronic phase CML. High-risk stem cell transplant remains the only viable option in blast phase, but outlook is grim even for the strongest patient. Apart from that, Melo raised the question how cured patients really are after stem cell transplant — even in the case when they survived the transplant and achieved complete absence of CML.

With the prospect of having generic Imatinib in 2015 and 2016 in many markets, some presentations this year seemed already to take account of new market dynamics that will arise. In many talks with experts, you could feel that Imatinib might get a second rise, or might remain first line treatment in many less well-off countries for a while. Current findings on assessing early response to Imatinib and early switching to more powerful second generation drugs in case of of suboptimal response might become even more relevant.

Patient Advocacy at ASH

Other than the EHA Annual Meeting, the ASH congress features no dedicated sessions on patient advocacy topics within the scientific programme. About two dozen patient advocates from the areas of leukemia, myeloma and lymphoma, well-connected in strong global networks, attended ASH 2011. This year’s patient advocates at ASH came from all across the world, including USA, Canada, Israel, Germany, UK, Spain, The Netherlands, Argentina, Venezuela, India, China, Australia, New Zealand and Malaysia, just to name a few countries.

Patient advocacy in haematology has evolved largely over recent years from being ‘patient support groups’ to being globally operating advocacy networks that closely collaborate with researchers, clinicians and industry – not only to learn about newest results of clinical trials and to meet world leading experts, but also to contribute to clinical trials, and to support the definition research priorities based on a unique insight on patient needs.

Patient advocates were particularly pleased that Dr. Andreas Hochhaus’ presentation in the CML education session drew special attention to the special role of patient advocates. “The CML community is an outstanding example of global patient advocacy – not to be seen in many other cancers,” Hochhaus said, “Patient advocates have become an independent, strong community, credible partners, advisors of clinicians, research projects and industry, as well as a strong political voice”.

Read more about CML at ASH 2011 in the following articles:

A more detailed report on the CML Education Session, the iCMLf Forum for physicians from emerging countries, clinical updates on the Nilotinib, Dasatinib, Bosutinib, Ponatinib, DCC-2036, Imatinib-Interferon combination, STOP studies, as well as some studies on CML and diabetes or fatigue are available on the CML Advocates Network .

About the author:

Jan Geissler is founder and managing director of Patvocates, acting in the area of cancer policy, patient advocacy and social media. After his studies (diploma in Business Management in the UK and Germany), Jan held various managerial positions in telecommunications and media industry think tanks before he focused his professional life on patient advocacy in 2008. Being a leukemia survivor who participated in various clinical trials himself, Jan founded the online patient community Leukämie-Online/LeukaNET in 2002 which is one of the most frequented online platforms for leukemia patients on the German speaking Internet today. In 2003, he co-founded the European Cancer Patient Coalition (European umbrella association of more than 300 cancer patient groups) and became its first full time director 2008. In 2007, Jan also co-founded the CML Advocates Network which is connecting 62 leukaemia patient groups from 49 countries on all continents today. He is a patients’ representative in various steering committees and advisory boards, acting e.g. as Secretary of the European Forum for Good Clinical Practice (EFGCP), in the EU Committee of Experts for Rare Diseases (EUCERD), in the ESMO Patient Working Party, in the ECCO Patient Advisory Committee, in the Editorial Board of the Journal of European CME, in the Institutional Review Board of EORTC, in the International CML Foundation, and in the External Advisory Board of the University Clinic of Jena. He also acts as an independent external EU expert.

You can follow Jan on Twitter: @jangeissler and view his LinkedIn profile here.

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