2012 American Society of Hematology (ASH) Annual Meeting

Professor John Gribben from Barts and The London Trust Cancer Centre, UK, is joined by Professor Peter Hillman from St James’s University Hospital, Leeds, UK, and Professor Kanti Rai from Long Island Jewish Medical Center, New York, USA, at ASH 2012 to talk to ecancer.TV about the exciting times being witnessed in CLL and the new data presented at the meeting. Professor Rai points to the “astounding” advances that have been made in CLL over the past 4-5 years based on improved understanding of the molecular biology of the disease, eg, the B-cell receptor and signalling pathways, that have led to the development of the PTK inhibitors and the PI3 kinase inhibitors. These new drug groups have given previously refractory patients new hope although Professor Rai comments on the caution still required concerning durability of response with ibrutinib and GS1101 as single versus combination agents. He also comments on the chemo-free approach to treatment and when this might be an appropriate therapeutic option. Professor Hillman notes the impressive and sustained response rates seen with some of these newer agents, and comments on the hope of cure of CLL in the future. Professor Hillman also notes the promise for the combined use of monoclonal antibodies with newer agents. The experts discuss the importance of educating patients on the expected response to newer agents, eg, on speed of response and lymphocytosis, and note from new data presented at ASH 2012 that many questions remain on the mechanism of action of newer agents. They also comment on promising new data being presented with Bcl-2 inhibitors and the challenge of getting all the new agents into logical clinical trial development programmes to speed effective agents to market as safely and rapidly as possible. Finally, the experts discuss the importance of the variety of patients being treated in clinical trials, eg, elderly, younger fitter patients and previously refractory patients.

Professor Michel Delforge from Catholic University, Leuven, Belgium, talks to Professor Meletios Dimopoulos from University of Athens, Greece, for ecancer.TV about multiple myeloma (MM). Noting the 700 abstracts on MM presented at ASH 2012, the experts discuss key findings and their implications to clinical practice. Professor Dimopoulos points to the pomalidomide abstracts as being of great interest to the MM community, including the long-term follow-up with over 300 patients, the pomalidomide data with low-dose vs. high-dose dexamathasone in refractory patients, and the pomalidomide data with numerous newer agents. Also data with the oral proteasome inhibitors, such as MLN9708, and novel monoclonal antibody agents, such as daratumumab. Professor Dimopoulos comments on the use of newer agents in the near future outside of the context of the clinical trial setting, focusing on carfilzomib and pomalidomide which are closest to market in Europe. The use of these agents in combination with others in refractory patients is discussed, as well as toxicity comparisons between pomalidomide and lenalidomide. The experts discuss in which patients to best use the novel monoclonal antibodies, such as elotuzumab, ie, in the front-line or refractory setting. Also, the hot topic in MM of the value and use of maintenance therapy in specific patients, and current use of bisphosphonates in patients with MM following the recent MRC9 data. The experts also discuss the important issue of effective management of MM in older patients (fit and frail), and the use of newer agents in this patient population.

Professor Gareth Morgan from The Royal Marsden, UK, talks to ecancerTV about how far treatment in myeloma has come over the past decade. Also where it is likely to go in the coming years as the use of newer agents are fine-tuned to further improve outcomes. He focuses on new data from ASH 2012 such as maintenance treatment with lenalidomide and bortezomib, and notes how newer agents have considerably improved patients’ quality of life. The challenge of whether to use single or combination agents remains, although Professor Morgan notes the additional challenge of toxicity in older patients with the use of combination agents. He points to the data on quadruplets of therapy presented at ASH 2012, and questions the use of this over triplets of therapy. Professor Morgan looks forward to the increased use of treatments according to laboratory sub-types, for example, using profiling to characterise mutational landscapes and sequencing to prevent the emergence of resistance in myeloma.

Professor John Gribben from Barts and The London Trust Cancer Centre, UK, is joined by Professor Myron Czuczman, Roswell Park Cancer Institute from Roswell Park Cancer Institute, New York, USA, and Professor Wolfram Brugger from Villingen-Schwenningen, Germany, at ASH 2012 to talk to ecancer.TV about hot topics in lymphoma from ASH 2012. Professor Czuczman points to the promise with lenalidomide in combination, eg, in indolent lymphomas, and data with new agents such as GS-1101, ibrutinib, PTK inhibitors and PI3K inhibitors. He also comments on the chemo-free approach to treatment and outlines some of these regimens in on-going clinical trials. Professor Czuczman also notes the importance of determining the order of therapies given, and of long-term follow-up in clinical trials.

Professor Gert Ossenkoppele from VU University Medical Center talks to ecancer TV about the treatment of acute myeloid leukaemia (AML) in elderly patients. Professor Ossenkoppele notes that standard treatment for elderly patients has mostly stayed the same in the last 30 years. Thus there is an urgent medical need for improvements in this patient group. In contrast, improvements have been made in treatments for younger patients, to whom more intensive treatments can be given. Many promising drugs interfering with the signal transduction pathways of AML cells are currently in phase I and II clinical trials, for example, trials involving gemtuzumab, a monoclonal antibody against anti-CD33. Data with tipifarnib, a farnesyltransferase inhibitor, are also outlined. Professor Ossenkoppele notes that epigenetic modulation of AML cells provides another potential avenue of treatment, with decitabine showing a survival benefit in elderly patients, and the potential place of this drug in therapy is addressed. Furthermore, the promise of allogenic stem cell transfers in the elderly using a reduced intensity conditioning regimen is outlined. Molecular prognostic tools could also be used to help treatment decision-making in older patients.

Professor Keith Stewart from the Mayo Clinic Arizona (Phoenix/Scottsdale, USA) talks to ecancer.TV about the use of new agents to treat myeloma. Professor Stewart notes new data on the use of carfilzomib, a drug recently FDA approved, and pomalidomide, with both drugs showing encouraging response rates. Professor Stewart then discusses the use of new agents against myeloma. Unlike other cancers, there are as yet no monoclonal antibody or kinase inhibitors used against this disease. Professor Stewart explains that data on many such agents were presented at this meeting. The two monoclonal antibodies, elotuzumab (anti-CS1 antibody) and daratumumab (anti-CD38 antibody), are most mature in their development and, when used in combination therapies, show impressive response rates. Professor Keith also outlines the data on two kinase inhibitors: ARRY-520 (a kinesin spindle inhibitor) and dinaciclib (a CDK inhibitor) both show about 15% single agent response rate. Professor Stewart then discusses cereblon, a specific target for thalidomide, lenalidomide and pomalidomide. He explains that measuring cereblon as a biomarker could help to predict response. Several large phase III clinical trials will mature in the coming year, including oral agents, and Professor Stewart summarises them and notes on drug costs and convenience. Finally, Professor Stewart explains that myeloma research has traditionally been divided into younger transplant-eligible patients and older patients who require a less aggressive approach. However, he notes that he has recently witnessed a blurring of this distinction, with elderly patients now receiving more aggressive treatment with good outcomes.

Professor Matti Aapro from Genolier, Switzerland, talks to ecancerTV about advances in anaemia management in cancer patients receiving chemotherapy over the past few years. He notes the challenges in managing these patients, and gives an overview of the results of analyses with ESAs in terms of safety, as well as recommendations for their use. He also notes the potential benefits of using iron in selected patients. Professor Aapro outlines the possible role of blood transfusions in anaemia in oncology, and points to new data presented at ASH 2012 and comments on how these data compare to data presented at ASH 2011. Professor Matti Aapro also summarises the latest data on tumour progression.

rofessor John Gribben from Barts and The London Trust Cancer Centre, UK, is joined by Professor Myron Czuczman, Roswell Park Cancer Institute from Roswell Park Cancer Institute, New York, USA, and Professor Wolfram Brugger from Villingen-Schwenningen, Germany, at ASH 2012 to talk to ecancer.TV about hot topics in lymphoma from ASH 2012. Professor Czuczman points to the promise with lenalidomide in combination, eg, in indolent lymphomas, and data with new agents such as GS-1101, ibrutinib, PTK inhibitors and PI3K inhibitors. He also comments on the chemo-free approach to treatment and outlines some of these regimens in on-going clinical trials. Professor Czuczman also notes the importance of determining the order of therapies given, and of long-term follow-up in clinical trials. Professor Brugger notes the need for combination regimens with newer agents and the challenge of finding which combinations work best. Professor Brugger also talks about the use of bendamustine in combination with some of the novel agents presented at ASH 2012, eg, NHL1 data. The experts emphasise the need for study investigators to get together post-ASH 2012 to co-ordinate the way forward in clinical trials following the wealth of new data. They also comment on the clinical, safety, ethical and economic consequences of long-term treatment in lymphoma, on the value of drug-free holidays, on compliance issues with new oral agents and on finding the balance between efficacy, toxicity and quality of life in lymphoma management. They discuss data presented for the newer treatments in different sub-types of lymphoma, eg, mantle cell lymphoma. Also on advances with targeted therapies, with summaries of data on new antibodies to direct therapies to the tumour cells. They discuss the important balance between aggressive vs. less aggressive therapy in different patients, and the future possibility of cure vs. long-term remission. Finally, the experts emphasise the palpable excitement in lymphoma from ASH 2012 and comment on where this might lead to.

Dr Maria Victoria Mateos from Salamanca, Spain, gives ecancerTV an overview of multiple myeloma (MM) noting advances due to the introduction of novel agents, such as bortezomib, lenalidomide and pomalidomide. She outlines the improved outcomes (PFS and OS) observed with the use of combination agents, and the management of toxicities, such as thromboembotic events, with newer agents. Dr Mateos comments on the role of stem cell transplants with the newer agents in terms of when and how agents should be used in younger and older patients. Focusing on optimisation of newer agents in older patients, Dr Mateos highlights the value of weekly vs. continuous therapy as well as low- vs. high-dose therapy. Finally, Dr Mateos summarises her views on the leading novel agents for use in combination. With several novel drugs and on-going clinical studies, it is expected that clinical practice will change over the coming years as more data are collected. Dr Mateos encourages the entry of MM patients into future clinical trials.

Professor Gareth Morgan from The Royal Marsden, UK, talks to ecancerTV about how far treatment in myeloma has come over the past decade. Also where it is likely to go in the coming years as the use of newer agents are fine-tuned to further improve outcomes. He focuses on new data from ASH 2012 such as maintenance treatment with lenalidomide and bortezomib, and notes how newer agents have considerably improved patients’ quality of life. The challenge of whether to use single or combination agents remains, although Professor Morgan notes the additional challenge of toxicity in older patients with the use of combination agents. He points to the data on quadruplets of therapy presented at ASH 2012, and questions the use of this over triplets of therapy. Professor Morgan looks forward to the increased use of treatments according to laboratory sub-types, for example, using profiling to characterise mutational landscapes and sequencing to prevent the emergence of resistance in myeloma.

Professor Mathias Rummel from Giessen, Germany, talks to ecancer.TV about the current management of indolent lymphoma with chemotherapy and rituximab, and rituximab maintenance, highlighting the limitations of this regimen. He goes on to outline potential new agents for indolent lymphoma, for example, promising early data with obinutuzumab (GA11),GS-1101 and ibrutinib used in combination with existing therapy, as well as some promise shown as single agent therapy. He also discusses other potential targets in indolent lymphoma, and summarises data on the use of interferon. Professor Rummel comments on the toxicities with these newer agents, and the importance of balancing frequency and duration of therapy with toxicity. He also emphasises the importance of focusing on quality of life in the management of this condition, commenting on the BRIGHT study.