ASH 2015

Prof Le Gouill (University Hospital of Nantes, Nantes, France) and Prof Rule (Derriford Hospital, Plymouth, UK) review the data and opinions arising from ASH 2015 about the treatment of mantle cell lymphoma (MCL) for ecancertv. The two experts consider a range of topics including the place of new agents with the best combinations and sequences for utilising them. The predictive power of FDG-PET parameters at diagnosis and after patients with MCL interim results from the LyMa-PET project. They discuss ibrutinib versus temsirolimus and the results from a phase III, international, randomised, open-label, multicentre study in patients with previously treated mantel cell lymphomas. They also consider the potential role of MRD status as a prognostic marker for MCL in the future.

Prof Tyner talks to ecancertv at ASH 2015 about his research looking at using functional drug screening to guide personalised cancer therapy. Prof Tyner’s lab has developed ex vivo functional screening platforms that can be applied directly to primary specimens from patients with haematological malignancies to identify candidate therapies on an individualised basis. These assays use panels of drugs and so can provide information about the specific drugs and even which combinations of drugs that the patient’s tumour cells are most sensitive to.

Prof Gribben (Queen Mary University of London and Barts Cancer Institute, London, UK), Prof Stilgenbauer (University of Ulm, Ulm, Germany), Dr Tedeschi (Azienda Ospedaliera Niguarda Cà Granda Milano, Milano, Italy) and Dr Thornton (Royal College of Surgeons, Dublin, Ireland) discuss the latest data on chronic lymphocytic leukaemia from ASH 2015. The experts cover the RESONATE-2 trial, which compared ibrutinib versus chlorambucil in the treatment of elderly patients who had not received any prior treatment. Efficacy and tolerance data from the trial are set to have a significant impact on CLL treatment for the elderly, it is observed. The panel also discuss data on venetoclax, an oral, targeted drug that inhibits Bcl-2 - a protein that regulates natural cell death. This new agent is a promising option for the very difficult-to-treat CLL patient population characterised by the presence of the 17p deletion. The GREEN study is also mentioned by the panel. This trial studied the combined effects of the glycoengineered type II anti-CD20 monoclonal antibody obinutuzumab with bendamustine in treatment naiive CLL. Finally the panel talks about risk stratification and using known pathways to stratify patients in combination with individual patient characteristics.

Prof Despotovic talks to ecancertv at ASH 2015 about the results of a study that looked for genes that may be involved in the development of chronic immune thrombocytopenia (ITP) in children using whole exome sequencing. Historically, chronic ITP has not been thought of as a genetic or inherited disease, Dr Despotovic says. The results of the study she presented at ASH 2015 showed that genetic anomalies can be found in children with the disorder. These anomalies include changes in the gene encoding interferon-alpha 17, which is involved in the activation of regulatory T cells and TGF-β signalling. The hope is that these findings will help researchers understand ITP biology better to enable the identification and stratification of patients and improve treatment by avoiding unnecessary toxicity.

Prof Khorana talks to ecancertv at ASH 2015 about current practice patterns and patient persistence on anticoagulant treatments for cancer-associated thrombosis. In the interview he describes a study that looked at almost 3,000 patients with cancer who were newly diagnosed venous thromboembolism (VTE) and had received anticoagulant treatment in the outpatient setting. Guidelines recommend that 3–6 months of a low-molecular-weight heparin (LMWH) be given, but it is not clear if this should be continued beyond 6 months. In this real-world practice setting 25% of patients were treated with a LMWH and 18.7% received LMWH or warfarin. A further 29% had been given warfarin and 24.1% had been given the newer oral anticoagulant rivaroxaban. On average the median duration of treatment was 3.29 months for LMWH, 7.76 months for LMWH/warfarin, 8.12 months for warfarin, and 7.92 months for rivaroxaban. Persistence to the initial therapy were a respective 37%, 60%, 62%, and 61% at 6 months, dropping to 21%, 37%, 34%, and 36% at 12 months. In addition more patients initially taking LMWH were found to have switched to another anticoagulant compared to patients who had been started on warfarin or rivaroxaban.

Prof Khorana talks to ecancertv at ASH 2015 about a randomised trial looking at the outpatient use of dalteparin for the prevention of thrombosis in cancer patients at high risk of venous thromboembolism (VTE). Several years ago Dr Khorana and colleagues developed an algorithm for assessing how likely patients with cancer were to develop VTE while being treated with chemotherapy. This takes into account several factors such as the site of the cancer, the platelet and leukocyte counts before chemotherapy is given, the level of haemoglobin and the patient’s body mass index. In the current trial, patients with a high risk for VTE (Khorana score ≥3) who were initiating a new systemic chemotherapy regimen were screened for VTE, If negative for VTE, patients were randomised to either self-inject the low molecular weight heparin dalteparin daily or to no prophylactic anticoagulation for 12 weeks. Thromboprophylaxis versus no thromboprophylaxis was associated with a non-significant reduced risk of VTE and rates of major bleeding and overall survival were similar. There was an increased risk of clinically relevant bleeding, but the study was underpowered. There is a validated risk assessment tool and it can be used to find patients at the highest risk that may benefit from anticoagulation with self-injected low-molecular-weight heparin Dr Khorana observes.

Dr Gökbuget talks to ecancertv at ASH 2015 about the long-term outcomes of patients with minimal residual disease positive (MRD ) B-cell precursor acute lymphoblastic leukaemia (ALL). Specifically, she highlights the findings of an international, multicentre phase II study in MRD ALL in which approximately 80% of patients achieved a complete MRD response, with no detectable disease after just 4 weeks of treatment with blinatumomab. The median overall survival was 36 months, which is a big improvement, and the median remission duration and relapse-free survival was 18 months and more, Dr Gökbuget says. The results suggest that treating MRD ALL before patient relapse can have a big effect on long term outcomes and that all clinicians should measure MRD, she suggests.

Catch up with the latest in haematology-oncology from the 57th American Society of Hematology Meeting in Orlando.

Dr Sekeres talks to ecancertv at ASH 2015 about a North American study (SWOG S1117) that tried to expand the treatment options for patients with higher risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML). There are few treatments available to treat patients with higher risk MDS and CMML and these have a limited impact on outcome, with around a 35% overall response rate (ORR) to azacitidine when it is used alone. The SWOG S1117 looked at adding the immunomodulatory lenalidomide or the histone deacetylase inhibitor vorinostat to azacitidine to see if ORR could be improved versus azacitidine monotherapy. The ORR and overall survival was similar for azacitidine monotherapy compared to the combination arms in patients with higher risk MDS. However, the ORR was significantly higher than the monotherapy when lenalidomide was added to azacitidine in patients with CMML. Dr Sekeres comments that dose reductions in the combination arms might have played a role in the somewhat disappointing findings. Data will need to be pooled to see if there are patient subgroups who might particularly benefit from the combination therapies.

Dr Mukherjee talks to ecancertv at ASH 2015 about a study looking at the risk of myelodysplastic syndromes (MDS) in patients treated with radioactive iodine for thyroid cancer. The study used a novel program to query all the Surveillance Epidemiology and End Results (SEER) registries in the USA to identify over 132,000 patients treated for thyroid cancer between 1973 and 2011. Of these 53% underwent surgery alone and 45% had surgery combined with radioactive iodine treatment. The remaining 2% had external beam radiotherapy followed by adjuvant radioactive iodine treatment. Patients who were treated with radioactive iodine had a statistically significantly increased risk of developing MDS within the first 2 years of exposure versus those who underwent surgery alone. The respective relative risk of MDS was 5.8 versus 1.9. The risk for MDS dropped to baseline rates after 2 years but there was a trend to increase again after 12 years. There is a low, but real risk of developing MDS following exposure to radioactive iodine for thyroid cancer, Dr Mukherjee observes. The reason for this is not known, but it is worth having a frank and free discussion with the patients to ensure they know about this potential risk of their thyroid treatment.

Dr Gay talks to ecancertv at ASH 2015 about the long-term results of an open-label, phase III trial in which young (

Dr Stewart talks to ecancertv at ASH 2015 about the ENDEAVOR study that has demonstrated superiority of carfilzomib over bortezomib in patients with relapsed and refractory multiple myeloma. Carfilzomib is a selective proteasome inhibitor approved in many countries for the treatment of relapsed and refractory multiple myeloma. ENDEAVOR was a randomised, phase III study that involved more than 900 patients who were treated with carfilzomib or bortezomib in addition to dexamethasone. The primary results demonstrated a clinically meaningful and statistically significant two-fold improvement in the median progression-free survival was achieved when carfilzomib was used rather than bortezomib (18.7 vs 9.4 months). For patients with multiple myeloma who have one to three prior relapses carfilzomib “is really the proteasome inhibitor of choice,” Dr Stewart suggests.

Prof Tarella talks to ecancertv at ASH 2015 about an international phase II trial that shows response to rituximab induction is a predictive biomarker in post-transplant lymphoproliferative disorder (PTLD) and allows successful treatment stratification. He also discusses a long-term survey of 597 patients, showing that life expectancy in follicular lymphoma is mainly determined by response to first-line treatment.

Prof Martinelli talks to ecancertv at ASH 2015 about the effects of the tyrosine kinase inhibitor blinatumomab in patients with Philadelphia-positive (Ph ), B-cell precursor acute lymphoblastic leukaemia (ALL) who had relapsed or who were not responding to their current treatment regimen. This is a very rare population of patients in a very rare disease, Prof Martinelli observes, which is important because there are few options once treatment with tyrosine kinase inhibitor therapy fails and the prognosis of patients is rather dismal. Results from the Phase II, single-arm, multicentre ALCANTARA study, however, suggest there could be a benefit of using the bispecific T-cell engaging (BiTE®) antibody construct blinatumomab.

Prof Moreau presents, at a press conference at ASH 2015, results from the phase III Tourmaline-MM1 study. Ixazomib, an investigational oral proteasome inhibitor, in combination with lenalidomide and dexamethasone, significantly extends progression-free survival for patients with relapsed and/or refractory multiple myeloma.

Prof Maury presents, at a press conference at ASH 2015, results of the GRAALL-R 2005 study in which the addition of rituximab to standard chemotherapy was found to improve the outcome of adult patients with CD20-positive, Ph-negative, B-cell precursor acute lymphoblastic leukaemia (ALL). The primary endpoint of event-free survival was increased from 52% with standard chemotherapy to 65% at 6 years when rituximab was added, Dr Maury says. Overall survival was about 60%. The latter appeared higher if patients who had received an allogeneic stem cell transplant at the time of their first complete remission were censored from the analysis.

Prof Stilgenbauer talks to ecancertv at ASH 2015 about the results of an international multicentre phase II study that evaluated the use of the anti-Bcl2-targeting therapy venetoclax as monotherapy in patients with very high-risk relapsed or refractory chronic lymphocytic leukaemia (CLL). All of the 107 patients that participated in the trial had CLL with the 17p deletion which is known to confer a worse prognosis than if the deletion is not present. The overall response rate to venetoclax monotherapy was 79.4% and the first-in-class agent induced deep remissions, including complete remission and undetectable minimal residual disease, to a degree that has been unheard of before now, Prof Stilgenbauer says in the interview. He notes that venetoclax was very well tolerated but that its use needs careful handling as it induces remission very rapidly.

Prof Moreau talks to ecancertv at ASH 2015 about results from the phase III Tourmaline-MM1 study in which ixazomib, an investigational oral proteasome inhibitor, was used in combination with lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma. The results showed that the once-weekly triple oral combination significantly extended progression-free survival when compared to placebo plus lenalidomide and dexamethasone. Prof Moreau notes in the interview that ixazomib is already approved for use in the USA and that once it is available in Europe clinicians should consider offering the all-oral combination tested in the trial to their patients.

Dr Plesner presents, at a press conference at ASH 2015, updated results of a phase I/II study (GEN503) looking at daratumumab in combination with lenalidomide and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma.

Prof Stilgenbauer presents, at a press conference at ASH 2015, results of the pivotal international phase II study. Venetoclax monotherapy induces deep remissions, including complete remission and undetectable mrd, in ultra-high risk relapsed/refractory chronic lymphocytic leukaemia with 17p deletion.

Dr Abla talks to ecancertv at ASH 2015 about an international, retrospective study looking at the incidence of and predictors for early death in paediatric patients with acute promyelocytic leukaemia (APL). APL is a rare subtype of acute myeloid leukaemia (AML) in children, Dr Abla explains and although the prognosis for those affected has improved over the years, a small proportion of children still die very early on in the disease course. The study considered data on more than 700 children and found the overall incidence of early death was 6.3%. Results support the early oral use of all-trans retinoic acid (ATRA), Dr Abla suggests.

Dr Stone presents, at a press conference at ASH 2015, results from an international prospective randomised P-controlled double-blind trial. The findings shows the multi-kinase inhibitor midostaurin prolongs survival, compared with placebo in combination with daunorubicin/cytarabine induction, high-dose C consolidation, and as maintenance therapy in newly diagnosed acute myeloid leukaemia patients with FLT3 Mutations.

Dr Zelenetz presents, at a press conference at ASH 2015, results of a phase III randomised double-blind placebo-controlled study. Idelalisib plus bendamustine and rituximab is superior to rituximab alone in patients with relapsed/refractory chronic lymphocytic leukaemia.

Dr Nimer talks to ecancertv at ASH 2015 about using epigenetics to treat haematological malignancies. Epigenetics can be used to interfere with cancer cells, forcing them to change their identity and behave like a normal cell. Dr Nimer explains how drugs are being developed to target some of the enzymes that are involved in important cancer processes such as self-renewal and differentiation. The combination of epigenetic approaches with immunotherapies such as the checkpoint inhibitors is potentially exciting, he observes. Immunotherapy can expose the cancer to the immune system but epigenetics can allow gene products to be expressed for the first time on a cancer cell that can then be the target of immunotherapies.

Dr Hromas talks to ecancertv at ASH 2015 about highlights from the targeted blood cancer therapies press conference that he chaired. The research presented at the press conference not only illustrated that immense progress has been made in the treatment of haematological malignancies, but also that the future lies in a more genetically driven and increasingly personalised approach. Dr Hromas comments that this is an exciting time for haematology-oncology practice.Dr Hromas comments that this is an exciting time for haematology-oncology practice.

Dr Tedeschi presents, at a press conference at ASH 2015, results from the international, randomised phase III study of ibrutinib versus chlorambucil in patients 65 years and older with treatment-naïve chronic lymphocytic leukaemia.

Dr Zelenetz talks to ecancertv at ASH 2015 about results of a phase III randomised, double-blind, placebo-controlled study that investigated whether adding idelalisib to standard treatment for relapsed or refractory chronic lymphocytic leukaemia (CLL) would be better than the standard treatment alone. Idelalisib is a first-in-class oral inhibitor or PI3k delta that is approved for use in combination with rituximab for the treatment of patients with relapsed CLL. It is also approved as first-line treatment for CLL patients with the 17p deletion or TP53 mutation who are not suitable for chemo-immunotherapy. The phase III trial included 416 patients who were randomized to receive the standard regimen of bendamustine plus rituximab with or without idelalisib. Results showed a significantly longer progression-free survival with the addition of idelalisib (23 vs 11 months).

Dr Maury talks to ecancertv at ASH 2015 about a randomised trial looking at the use of rituximab in addition to standard chemotherapy to treat patients with a specific subtype of acute lymphoblastic leukaemia (ALL). Rituximab is a routine treatment for B-cell non-Hodgkin’s lymphoma and mature B-cell ALL but there is no randomized trials evidence to support it’s use in B-cell precursor ALL. Prof Maury presented the results of the GRALL-R 2005 study that looked at the addition of rituximab to chemotherapy in more than 200 adult patients (median age 40 years) with CD20-positive, Ph-negative, B-cell precursor acute lymphoblastic leukaemia. The primary endpoint of event-free survival was increased from 52% with standard chemotherapy to 65% at 6 years when rituximab was added, Dr Maury says. Overall survival was about 60%. The latter appeared higher if patients who had received an allogeneic stem cell transplant at the time of their first complete remission were censored from the analysis.

Dr Lozano talks to ecancertv at ASH 2015 about overcoming the barriers of the p53 dysfunction to cure haematological malignancies. p53 is a potent tumour suppressor gene that activates many other genes involved in a cell's response to stress or DNA damage. Such responses may include apoptosis, arrest of the cell cycle or biological aging (senescence). However, genetic changes in p53 are common in all cancers, Dr Lozano explains. p53 can be deleted but missense mutations occur much more frequently (approximately 70% of genetic alterations). These mutations not only “cripple p53” but also give it “gain-of-function activities” that contribute to more aggressive tumours with increased metastatic properties. In the interview, Dr Lozano discusses how understanding the mechanisms by which mutant p53 exert these gain of function activities could be use to treat haematological malignancies.

Dr Townsley talks to ecancertv at ASH 2015 about adding eltrombopag to standard immunosuppressive therapy for aplastic anaemia in previously untreated patients. Eltrombopag was originally developed to increase platelet counts in patients with chronic immune thrombocytopenia (ITP) but it was found to also increase white and red cell counts. This was logical in hindsight, Dr Townsley observes in the interview. Although it is licensed for the treatment of refractory aplastic anaemia in Europe, eltrombopag is only approved for use in ITP in the USA and further study data were needed. The study presented by Dr Townsley aimed to provide evidence that eltrombopag could be used in aplastic anaemia setting and included 92 patients with the rare disease. Results showed a clear benefit of adding eltrombopag to standard immunosuppressive therapy of horse antithymocyte globulin (hATG) and cyclosporine versus the immunosuppressive therapy alone. Haematological overall response rates were 80% and 85% at 3 and 6 months, respectively, and highest if eltrombopag was given on the first day of immunosuppressive therapy as opposed to 2 weeks after and continued for either 3 or 6 months. Overall survival is 99%, Dr Townsley highlights, as only one patient has died while in the study to date but follow up is short.

Dr Tedeschi talks to ecancertv at ASH 2015 about using ibrutinib to treat chronic lymphocytic leukaemia (CLL) in elderly patients. The majority of elderly patients poorly tolerate the most intensive immuno-chemotherapeutic regimens, so an alternate form of treatment is needed, she explains. Dr Tedeschi discusses the results of the Phase III RESONATE-2 study that enrolled 269 elderly (≥65 years), treatment-naïve patients with CLL or small lymphocytic lymphoma (SLL) who were randomized to receive either ibrutinib or chlorambucil. Compared to treatment with chloroambucil, treatment with ibrutinib rath was associated with better progression-free, overall and event-free survival and better overall response rates and haematological improvement.

Prof Marivi Mateos (University Hospital of Salamanca, Salamanca, Spain), Prof Meletios Dimopoulos (University of Athens, Athens, Greece), Dr Torben Plesner (Vejle Hospital, University of Southern Denmark, Vejle, Denmark) and Prof Sagar Lonial (Emory University School of Medicine, Atlanta, USA) discuss the latest data on multiple myeloma from ASH 2015. The panel discuss novel combination approaches to treat multiple myeloma, the role of monoclonal antibodies as single agents or in combination, and how to manage potential side effects. During the discussion the experts talk about several studies including the recent findings of a phase III trial looking at daratumumab monotherapy in heavily pretreated patients with relapsed or refractory multiple myeloma. Results from an update of the ELOQUENT-2 study of elotuzumab in combination with lenalidomide/dexamethasone in patients with relapsed or refractory multiple myeloma and the updated results of the Phase I GEN503 study are also highlighted, both of which made an impact at the meeting. They also discuss a study investigating the use of daratumumab in combination with lenalidomide and dexamethasone in patients with relapsed or relapsed refractory multiple myeloma. The combination of daratumumab with pomalidomide and dexamethasone in the same setting is also discussed. Finally they look at what the future may hold in the ever-changing treatment landscape of multiple myeloma.

Dr Landier presents, at a press conference at ASH 2015, results from a study looking at 6-Mercaptopurine (6MP) intake during maintenance for childhood acute lymphoblastic leukaemia. The study was conducted by the Children's Oncology Group, comparing self-report and electronic monitoring.

Dr Cole presents, at a press conference at ASH 2015, results from a study looking at a genetic variant that signifies higher risk for avascular necrosis in children with acute leukaemia.

Dr Karol presents, at a press conference at ASH 2015, results from a study looking at genetic risk factors for the development of osteonecrosis in children under age 10 treated for acute lymphoblastic leukaemia.

Dr Saad Usmani (Carolinas Healthcare System, Charlotte, USA) and Prof Thierry Facon (Hospitalière et Universitaire, Lille, France) discuss the latest data from ASH 2015 daratumumab and elotuzumab and the potential role of these monoclonal antibodies in the treatment of multiple myeloma. Daratumumab was recently approved for use in the USA becoming the first monoclonal antibody to be licensed for the treatment of relapsed/refractory multiple myeloma. Dr Usmani presented data from a combined analysis of two studies in heavily pretreated MM patients the meeting showing that single-agent daratumumab could produce an overall response rate of 31%. Elotuzumab has also recently received approval from the US Food and Drug Administration for use in combination with two other therapies to treat people with multiple myeloma who have received one to three prior therapies. Long-term follow-up results of the ELOQUENT-2 study were presented at ASH 2015 showing that this monoclonal antibody can produce an effective and durable benefit.

Prof John Gribben (Queen Mary University of London and Barts Cancer Institute, London, UK) and Prof Stephan Stilgenbauer (University of Ulm, Ulm, Germany) discuss the latest advances in the treatment of chronic lymphocytic leukaemia (CLL) presented at ASH 2015 and share their opinions on treatment selection and considerations for different patients. Ibrutinib has previously been largely used as a treatment for high-risk patients with refractory CLL but data from the RESONATE-2 trial presented at the meeting by Dr Alessandra Tedeschi (Azienda Ospedaliera Niguarda Cà Granda, Milano, Italy) suggests that earlier use of the drug in treatment-naïve patients would also be of benefit.

Dr Despotovic presents, at a press conference at ASH 2015, results of a study looking at genes influencing the development and severity of chronic ITP identified through whole exome sequencing.

Dr Soff presents, at a press conference at ASH 2015, results from a quality assessment study looking at enoxaparin dose reduction for thrombocytopenia in patients with cancer.

Dr Raetz presents, at a press conference at ASH 2015, results from the Children's Oncology Group report into genetic and response-based risk classification. It has identified a subgroup of NCI high risk childhood B-lymphoblastic leukaemia.

Dr Chai-Adisaksopha presents, at a press conference at ASH 2015, results from a study looking at switching patients to warfarin after 6-month completion of anticoagulant treatment for cancer-associated thrombosis.

Dr Stock talks to ecancertv at ASH 2015 on a study that looked at genetic risk factors for the development of osteonecrosis in children aged 10 years or younger who were being treated for acute lymphoblastic leukaemia. The study, presented by Dr Seth Karol of St Jude Children's Research Hospital in Tampa, USA, showed that children who developed osteonecrosis were more likely to have genetic variants near a gene important to bone development (BMP7) and a gene important to fat levels in the blood (PROX1) than those who did not develop the bone disease.