EHA 2016

Prof Sacha talks to ecancertv at EHA 2016 about a study from the Polish Imatinib Generics Registry (PALG) investigating the effectiveness and safety profile of twelve imabtinib generics, compared to the brand name drug. He describes the regulatory background of generic drug availability in Poland, from production to costs, and how that is reflected in the wider field of pharmaceuticals. Overall, Prof Sacha reports that no generic imatinib drug is worse than the brand named version, and could be cheaply included in care.

Dr Fathi presents, at a press conference at EHA 2016, data from an ongoing phase I trial evaluating vadastuximab talirine (SGN-CD33A; 33A) in combination with standard therapies (azacitidine, decitabine) in older AML patients who have declined intensive frontline therapy. This combination was well-tolerated and yielded encouraging response rates in older AML patients.

Dr Toft presents, at a press conference at EHA 2016, the results of a study that found that adult survival of adult acute lymphoblastic leukaemia (ALL) is close to that of children and has markedly improved.

Dr McCarthy talks to ecancertv at EHA 2016 about a meta-analysis into the efficacy of lenalidomide (LEN) maintenance to treat multiple myeloma (MM) following high-dose melphalan and autologous stem cell transplant (HDM ASCT). LEN has proven efficacious in reducing disease progression, but these studies were not powered for overall survival (OS). In analysing data from 1,200 patients, gathered over three previous trials (IFM 2005-02, CALGB 100104 [Alliance], GIMEMA RV-209) that match the criteria (had patient-level data, had a control arm, and achieved database lock for primary efficacy analysis of patients with newly diagnosed MM receiving LEN post ASCT), Dr McCarthy reports that LEN maintenance significantly prolongs OS compared to control. He encourages LEN maintenance as the standard of care HDM ASCT, and introduces further studies into LEN as a single agent or as part of a therapeutic combination.

Dr Goff speaks with ecancertv at EHA 2016 about her research confirming the efficacy of CD19 chimeric antigen T-cells (CAR T-cells) in patients with advanced lymphoma, even following lower doses of chemotherapy than previously established. She describes her earlier research in which CD19 CAR T-cells were found to be effective with high dose chemotherapy, and that remission and recovery rates are maintained in this follow-up. Dr Goff describes neurological side-effects associated with CAR T-cell therapy have been transient, and expects that this balance of chemo-immunotherapy could be brought forwards towards clinical use.

Dr Jones presents, at a press conference at EHA 2016, an evaluation of data from 243 patients with del17p CLL who were combined from 3 ibrutinib clinical trials with half of the patients on study for 28 months or longer. The percentage of patients who responded to ibrutinib therapy (overall response rate) was 84%.

Dr Hazenberg presents, at a press conference at EHA 2016, details of her work looking at patients who are in remission from AML and about the discovery of antibodies that bind specifically to AML cells. The investigators found that U5 specific antibodies are ‘killer antibodies’ that kill AML blasts in vitro and (in a mouse model) in vivo.

Prof Meletios Dimopoulos presents, at a press conference at EHA 2016, the results of POLLUX, an open-label, randomised phase III study that evaluated the combination of daratumumab and lenalidomide and dexamethasone (daratumumab group) compared with lenalidomide and dexamethasone (control group) in patients with relapsed/refractory multiple myeloma.

Dr Richter presents, at a press conference at EHA 2016, the results of the EURO-SKI trial which sought to determine the proportion of patients keeping their therapy response after stopping TKIs and to the clinical and biological factors that predict successful TKI-stop. Results of the trial show that 62% of the patients still maintained treatment response (MMR) 6 months after stopping therapy.

Prof Topp presents, at a press conference at EHA 2016, the results of a single arm Phase II trials with blinatumomab which have shown that 43% of relapsed or refractory (r/r) ALL patients can achieve disease control.

Dr Metzeler presents, at a press conference at EHA 2016, a study that looked at sample pairs collected at the time of leukaemia diagnosis, and after chemotherapy while the patient was in remission, from 107 patients with AML. Patients with persisting mutations had a higher risk of subsequent disease recurrence compared to those with no persisting mutation.

Dr Katerina Machova Polakova talks to ecancertv at EHA 2016 about single nucleotide polymorphisms (SNPs) associated with response to first line treatment with imatinib for patients with chronic myeloid leukaemia (CML). She describes mutations in SLC regions that may represent genetic markers for CML, and the benefit to patients and caregivers alike in a fully informed choice of treatment, depending on probable response.

Dr Younes presents, at a press conference at EHA 2016, the results of the registrational trial, Checkmate 205, a Phase 2 evaluating nivolumab with classical Hodgkin lymphoma (cHL) — it was shown to be efficacious.

Prof Pemmaraju talks to ecancertv at EHA 2016 about SL401, a novel agent to treat blastic plasmacytoid dendritic cell neoplasms (BPDCN). He details the history of the disease and unusual constellation of symptoms, before introducing SL401 - a truncated diphtheria toxin attached to IL3, corresponding to over-expression of IL3R on BPDCN cell surface. In phase I and dose escalation trials, Dr Pemmeraju reports a significant response, with further trials now enrolling patients, and discusses the growing availability of immunopathogens. He also highlights the role of public engagement and social media in reaching healthcare providers and those affected by the disease, who may not otherwise know of this rare disease.

Dr Bolli talks to ecancertv at EHA 2016 about how his research using next generation sequencing techniques has uncovered potential oncogenic drivers linked to multiple myeloma. Numerous gene regions are notorious for their roles in cancer development, KRAS, BRAF, and p53. Here, Dr Bolli discusses some similarly implicated hotspots, acknowledging that further trials are needed to determine if any are significant biomarkers.

Dr Hazenberg speaks with ecancertv at EHA 2016 about anti-tumour antibodies isolated from AML patients who had been cured following autologous stem cell transplant (ASCT). She describes the process through which these antibodies were generated and identified., highlighting that they weren't selected by any assaying, but from a purely post-therapeutic response Dr Hazenberg believes this innate immune response could be transferable and applied in therapy. It could also inform the creation of future therapy, either through clearer understanding of the mechanistic process of this anti-tumour reaction, or in complement to other treatments including immunotherapy.

Dr Bezman talks to ecancertv at EHA 2016 about a novel immunotherapeutic combination tested in mouse models, combining PD-1 blockade therapy with elotuzumab, a SLAMF7 binding monoclonal antibody. SLAMF7 is overexpressed on the surface of tumour cells, and is also involved in the recruitment of NK T-cells. She reports that by combining these checkpoints inhibition with innate immune response, tumours are significantly reduced. Dr Bezman also comments on PD-1 targeting in solid and liquid tumours, and introduces ongoing clinical trials for advancing these mouse model results to human trials, which are currently recruiting patients.

Dr Daver talks to ecancertv at EHA 2016 about results from a phase I/II study combining established leukaemia therapeutic decitabine with vosaroxin. He summarises the shared aetiology of acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS), and gives his rationale for trialling vosaroxin, a first-in-class topoisomerase inhibitor, as a combinatorial agent alongside the standard course of decitabine. He reports findings from dose-establishing trials, and the improvement to median survival time, progression free survival and overall survival of patients.

Dr Richter talks to ecancertv at EHA 2016 about results from the EURO-SKI (Stopping Kinase Inhibitor) trial. Kinase inhibitors have become a core component of modern cancer therapy, with ibrutinib, sorafenib and entrectinib being among the most recently investigated. However, Dr Richter reports results from the EURO-SKI trial which indicate that up to 50% of chronic myeloid leukaemia (CML) patients could stop their therapy, with relapse-free survival reported at 6 month, 12 month and 3 year checkups. Dr Richter discusses the reasons why a patient may want to cease kinase inhibitor therapy, including associated side effects and cost, and also highlights the incidence to TKI withdrawal syndrome, a side effect that is not yet fully understood but which will be the subject of further research

Prof Peter Hillmen (Leeds Teaching Hospitals NHS Trust, Leeds, UK), Prof Paolo Ghia (Università Vita-Salute San Raffaele, Milan, Italy), Dr Chris Fox (Nottingham University Hospitals NHS Trust, UK) and Dr Constantine Tam (Peter MacCallum Cancer Centre, Melbourne, Australia) discuss the latest therapeutic advances in CLL from EHA 2016. First discussed was a cross-study analysis of treatment outcomes for patients with deletion 17P CLL treated with ibrutinib. The study demonstrated a remarkably consistent RR and had not yet reached median PFS (estimated three years), which surpasses results of previous therapies for del17p CLL and is better than anything seen pre-ibrutinib. The impact of ibrutinib in relapsed/refractory CLL was analysed within a real-world setting of nearly 3000 patients across 30 countries, which suggested that results observed in ibrutinib clinical trials are reproducible in clinical practice. A key consideration surrounding the use of ibrutinib is which line of therapy to use it in, following the EMA and FDA approvals for all patients with CLL. An analysis from PIII studies showed that patients who received ibrutinib in earlier lines of treatment as 1st or 2nd line therapy were less likely to progress and experienced better post-ibrutinib survival outcomes. This reinforces the belief that ibrutinib should be used more widely in earlier lines of therapy. Also discussed were trials involving Obinutuzumab (GA101) plus chlorambucil (Clb) or rituximab (R), showing that this combination significantly increased the length of PFS in elderly populations. The panel touched upon the use of venetoclax with new data being presented at EHA, leading them to conclude that combinations of biologics may be the way forward, such as ibrutinib and venetoclax. The panel concluded the discussion by debating what should be the standard of care (SOC), suggesting that FCR should remain the SOC for young patients with no comorbidities, but all the remaining patients should benefit from novel therapies in the first line setting. This argument may be decided by ongoing trials evaluating ibrutinib versus FCR.

Dr Bröckelmann talks to ecancertv at EHA 2016 to talk about the German Hodgkin Study Group analysis of patients with Hodgkin lymphoma who experience a late relapse of disease >5 years after diagnosis. He details the rate of late relapses identified among a cohort of over 5000 patients, and the challenge to distinguish them from secondary cancers. He encourages long-term surveillance of patients, especially from the vulnerable subtype of males with nodular lymphocyte predominant subtype treated for early stage favourable disease. Progression-free and overall survival in these patients seems to compare favourably with earlier relapses.

Prof Sierra talks to ecancertv at EHA 2016 about how patients therapy selection to treat acute myeloid leukaemia (AML) can be guided through risk factors determined through genetic analysis. He describes how informing patients and care providers of their risk stratification can craft personalised therapy and minimise the chances of failed treatment.

Prof Marivi Mateos (University Hospital of Salamanca, Salamanca, Spain), Prof Meletios Dimopoulos (University of Athens, Athens, Greece), Prof Paul Richardson (Dana-Farber Cancer Institute, Boston, USA) and Prof Phillip McCarthy (Roswell Park Cancer Institute, New York, USA) discuss the latest data on multiple myeloma from EHA 2016. Presented during the Presidential Symposium, the POLLUX data was an open-label, randomised PIII study of daratumumab, lenalidomide, and dexamethasone (DRd) versus lenalidomide and dexamethasone (Rd) in relapsed or refractory multiple myeloma (RRMM). Prof Meletios Dimopoulos outlines one of the key presentations from EHA 2016, showing a 63% reduction in the risk of progression/death and a doubling of CR for DRd vs Rd. The addition of daratumumab also increased the ORR for DRd vs Rd (93% vs 76%) and improved median PFS which was 18.4 months for patients receiving Rd and has not yet been reached in the daratumumab arm. This data led the panel to pose the question whether this could be considered “the most active treatment in this setting”, and with positive combination data also discussed from the CASTOR trial, concluding that combination therapies are having a positive impact on the MM landscape. A note of caution was expressed for triple refractory patients where combination therapy fails, so although treatment seems to be heading in the right direction, it has not yet answered some important and remaining clinical questions. Another study discussed looked at a meta-analysis of OS in patients with MM treated with lenalidomide (LEN) maintenance after high-dose melphalan and autologous stem cell transplant (ASCT). This large study demonstrated that LEN maintenance significantly prolonged OS vs placebo/no maintenance post ASCT, including in patients who achieved CR. This being the case, there are questions remaining for patients receiving this treatment with high risk genetic abnormalities. These trials show the therapeutic advances coming from EHA 2016, building anticipation for the future progress that can be made for treating patients with multiple myeloma.

Prof Naldini talks to ecancertv at EHA 2016 about a fragment of microRNA called miR-126, which has been found to regulate both haematopoietic stem cells (HSC) and B-cell acute lymphocytic leukaemia (B-ALL). He describes results generated from a mouse model with doxycycline-repressible miR-126 expression that, when engrafted with human B-ALL blasts, undergoes induced disease recovery and relapse, depending on over or under expression. Of these results, he notes that any modulation of miRNA-126 results in increased apoptosis and graft rejection in mice, confirming that human B-ALL depends on precise expression levels, and that imatinib treatment was less effective in miR-126 knockdown doses.

Prof Topp talks to ecancertv at EHA 2016 about blinatumomab to treat relapsed or refractory B-cell acute lymphoblastic leukaemia (rrALL). With results from the phase III TOWER study, he reports on media overall survival being almost doubled with blinatumomab compared to standard care, and that previous neurologic side effects associated with blinatumomab are found to be equal to those in patients receiving comparable chemotherapy, and with reduced risk of cytokine syndrome than CAR T-cell therapy.

Prof Naldini talks to ecancertv at EHA 2016 about the state of modern gene sequencing and gene editing patient care. Summarising applications of genetic therapies in haematological malignancies and beyond, Prof Naldini reviews their historic modalities and potential future roles in developing truly effective personalised therapies.

Dr Katerina Machova Polakova talks to ecancertv at EHA 2016 about single nucleotide polymorphisms (SNPs) associated with response to first line treatment with imatinib for patients with chronic myeloid leukaemia (CML). She describes mutations in SLC regions that may represent genetic markers for CML, and the benefit to patients and caregivers alike in a fully informed choice of treatment, depending on probable response.

Dr Lu talks to ecancertv at EHA 2016 about ponatinib, whose exact resistance mechanisms are not yet fully understood. Ponatinib overcomes TKI resistance (imatinib, nilotinib and dasatinib) that develops due to BCR-ABL1 kinase domain (KD) mutations including T315I. Dr Lu summarises her trial of determining TKI resistance in BCR-ABL1 cell line models to determine whether pre-exposure, over-exposure, or other novel mechanisms may lead ponatinib resistance, and the impact that has on subsequent treatments.

Professor Steven Le Gouill (University Hospital of Nantes, Nantes, France) and Professor Simon Rule (Derriford Hospital, Plymouth, UK) take a look at some of the key data coming out of EHA 2016 and the impact this could have on clinical practice. Following on from the RAY data presented at ASH in 2015, new data presented at EHA 2016 showed a pooled analysis from three ibrutinib studies (PCYC-1104, MCL2001 [SPARK] and MCL3001 [RAY]), which aimed to assess the impact of baseline factors on OS in patients with relapsed/refractory MCL. The study showed that traditionally poor prognostic factors e.g. blastoid histology, adversely impacted on OS and PFS, where patients with worse disease had a reduced response to ibrutinib compared to patients with a better prognosis, albeit with response rates being higher than those seen with other treatments. Additionally, this study demonstrated that in younger patients with fewer prior lines of therapy and a better prognosis, OS is significantly longer in ibrutinib-treated patients. With a higher CR and OS for patients taking ibrutinib first line compared to >1 prior line of therapy, this study provides compelling evidence for the use of ibrutinib as a first line treatment. On the topic of first line treatment, they also discussed the new ENRICH trial, which is still recruiting and will look at ibrutinib and rituximab verses ibrutinib and chemotherapy in MCL patients aged 60 years or older who haven’t received treatment.

Professor Simon Rule (Derriford Hospital, Plymouth, UK) and Professor Steven Le Gouill (University Hospital of Nantes, Nantes, France), discuss some of the most topical questions currently being asked across the MCL landscape at EHA 2016. Professor Le Gouill postulates whether Autologous Stem Cell Transplantation (ASCL) for young patients should still be considered standard of care outside of clinical trials, or if the emergence of new treatment options mean that ASCT is living its last years as a first line treatment option. Also discussed is the role of chemotherapy, and how if there is to be a paradigm shift in the treatment of MCL, new therapies must show an advantage without the use of chemotherapy. With the future of healthcare progressing towards personalised medicine, Professor Rule and Professor Le Gouill note that it is vital that future research in MCL keeps pace with the objective of predicting treatment response in patients.

Dr Tchernonog talks to ecancertv at EHA 2016 about plasmablastic lymphoma (PBL). First described in 1997 in the oral cavity of HIV patients, PBL is now recognised as a distinct, aggressive and rare entity of diffuse large B-cells lymphoma by the World Health Organization classification. Among patients from immunocompromised and non-immunocompromised arms of the LYSA group, she identifies a new subgroup of patients characterised by CD20-/CD138 immunophenotype. Dr Tchernonog summarised the treatment options available to these patients, including the combination of rituximab with chemotherapy, and expresses the need for further understanding of this rare disease, and its apparent biomarkers.

Prof Antic talks to ecancertv at EHA 2016 about thromboembolic events, a common risk facing lymphoma patients.Prof Antic talks to ecancertv at EHA 2016 about thromboembolic events, a common risk facing lymphoma patients. He describes how chemotherapy and disease increase the chances of such an event developing in patients, and the development of a prognostic score, ThroLy, to establish risk stratification for patients with up to 90.2% specificity. Given their frequency of these complications, Prof Antic advocates ongoing haematological analysis throughout patient admission, and anticipates further testing of ThroLy in wider applications. He describes how chemotherapy and disease increase the chances of such an event developing in patients, and the development of a prognostic score, ThroLy, to establish risk stratification for patients with up to 90.2% specificity. Given their frequency of these complications, Prof Antic advocates ongoing haematological analysis throughout patient admission, and anticipates further testing of ThroLy in wider applications.

Prof Gisselbrecht talks to ecancertv at EHA 2016 about the SCHOLAR-1 trial, identifying patient cohorts most likely to respond to aggressive diffuse large B-cell lymphoma (DLBCL). He describes patient selection from an initial pool of over 800 eligible responders, and the results from the trial including the surprising short term response followed by relapse among certain subgroups. Prof Gisselbrecht emphasises that these are initial results, with further analysis forthcoming.

Dr Schlegerberger talks to ecancertv at EHA 2016 about inherited risks for haematological malignancies such as leukaemia and the screening practices surrounding them. She describes the current landscape of genetic screening and counselling available to patients in Europe with particular attention to known causative mutations and how these can influence patient involvement and therapy over the course of their treatment. She advocates for widespread testing and patient engagement, urging more awareness raising among clinicians and patients.

Dr de Bock talks to ecancertv at EHA 2016 about the role of a conserved gene cluster called HOXA, and it's co-operative role in driving T-cell acute lymphoblastic leukaemia. He describes how HOXA mutations, especially HOXA9, are often concurrent with mutations in the cell cycle regulatory JAK pathway, and that the two of them together are strong drivers of oncogenesis. Dr de Bock also discusses how these pathways might be identified and regulated, giving example of the resequencing in patients that determined this genotype.

Dr Perrotti talks to ecancertv at EHA 2016 about micro RNAs (miR) which influence cell cycle progression of haematopoietic stem cells, and their role in modulating chronic myeloid leukaemia (CML). The JAK-STAT pathway is one of the most well known in regulating the cell cycle and growth, and Dr Perrotti discusses how miR-300 induction of activity can promote or silence leukaemia development.

Dr Fathi talks to ecancertv at EHA 2016 about an ongoing phase I trial that looks at the use of vadastuximab talirine (SGN-CD33A; 33A) in combination with standard therapies (azacitidine, decitabine) in older AML patients who have declined intensive frontline therapy.