ASH 2016

Prof Marivi Mateos (University Hospital of Salamanca, Salamanca, Spain) chairs an expert discussion on the latest in Multiple Myeloma (MM) for ecancertv at ASH 2016 in San Diego. With Prof Philippe Moreau (University Hospital of Nantes, Nantes, France), Prof Saad Usmani (Carolinas Healthcare System, Charlotte, USA) and Prof Heinz Ludwig (Wilhelminenspital, Center for Oncology and Hematology, Vienna, Austria). The discussion started by looking at newly diagnosed multiple myeloma patients, with data from the FIRST trial showing treatment with lenalidomide plus low-dose dexamethasone until disease progression improved outcomes for transplant-ineligible patients. Whilst PFS and OS were significantly prolonged, the incidence of cataracts seen in this patient population was noted. The panel then moved on to the relapsed/refractory setting (RRMM), with a focus on the Phase III POLLUX and CASTOR data, which recently have led to the FDA approvals of daratumumab in combination with either lenalidomide and dexamethasone (DRd) or bortezomib and dexamethasone (DVd) for patients with RRMM who have had at least 1 prior therapy. The updated CASTOR data shows that the treatment benefit of DVd was maintained, with the ‘best benefit’ seen in patients with 1 prior line of therapy. The updated POLLUX data also showed that responses with DRd were deep and durable, with these ‘practice changing’ results translating into significantly improved clinical outcomes vs Rd in 1-3 PL pts with RRMM. Leading on from this was the evaluation of Minimal Residual Disease (MRD) in the CASTOR and POLLUX trials, with these ‘outstanding’ results demonstrating that daratumumab -containing therapies are able to drive patients to deep levels of clinical response. ASH 2016 also saw data presented that analysed a subcutaneous formulation of daratumumab, which was well tolerated and achieved serum trough concentrations similar to or greater than intravenous (IV) daratumumab with a lower rate of infusion related reactions compared to IV daratumumab over a significantly shorter infusion time. It was noted that the SC formulation of daratumumab should be explored in future clinical trials. The discussion was rounded up with the mention of promising results with selinexor and the STORM trial, venetoclax as both a single agent and in combination, and the use of checkpoint inhibitors for the treatment of multiple myeloma patients.

Dr Davies speaks with ecancertv at ASH 2016 about the efficacy of treating follicular lymphoma with a fixed subcutaneous dose. He describes the safety profile of both treatment regimens, with non-inferiority being determined for subcutaneous delivery, though a significant benefit in cost, time and resource demand.

Dr Davies speaks with ecancertv at ASH 2016 about phase III trials of obinutuzumab, an anti-CD20 monoclonal antibody for the treatment of follicular lymphoma. He describes the influence of pre-treatment on tolerability, and draws comparison to rituximab based chemotherapy for efficacy, but notes concerns over toxicity management.

Dr Wei speaks with ecancertv at ASH 2016 about treating AML in elderly patients with venetoclax, a Bcl-2 inhibitor, and cytarabine (ara-c). He describes patient outcomes following venetoclax 600mg and low-dose cytarabine, with high response and complete remission rates. Dr Wei summarises subgroup analysis, and outlines how results maturing in the future will better inform any changes to practice.

Dr Alfonso Pierola meets with ecancer at ASH 2016 to discuss the clinical utility of next generation sequencing to determine actionable mutations in myelodysplastic syndrome. She describes how, while targeted therapies have been successful in other tumour types, only a small proportion of MDS patients sequenced had a known mutational driver that might justify their involvement in further clinical trials. Overall Dr Pierola describes the inclusion of sequencing as in its infancy for MDS, and looks forward to future development based on a refined pool of targets.

Dr Rambaldi speaks with ecancertv at ASH 2016 about the final results of the Northern Italy Leukaemia Group (NILG) trial combining paediatric-type therapy with minimal residual disease (MRD) review, and risk-oriented haematopoietic cell transplantation (HCT) in adult acute lymphoblastic leukaemia (ALL). The current paediatric-type therapy and MRD-based risk-oriented strategy was applicable to adults with ALL in a wide age range, with some limitations in patients over 60 years. MRD was essential in orientating the HCT choice in both standard risk and high risk patients and retained a major prognostic role in all patients. Optimizing the early MRD response with new immunotherapeutics and clarifying the role of HCT in MRD responsive very high risk patients are topics for future research.

Dr Montalbán Bravo meets with ecancertv at ASH 2016 to discuss the aetiology and prognostic outlook of pure erythroid leukaemia, a subset of acute leukaemia. He discusses the cell lineage of the disease, and describes sequencing data helping to form a greater genetic and biological understanding of PEL and its treatment choices.

Prof Garcia-Manero speaks with ecancertv at ASH 2016 about results from a phase II trial of pracinostat and azacitidine for elderly patients with acute myeloid leukaemia. He describes how, while negative results for the combination in treating MDS might be attributed to inappropriate dose levels, pracinostat is proving highly efficacious in treating AML with a promising outlook on further combinations in randomised trials.

Dr Montalbán Bravo speaks with ecancertv at ASH 2016 about two promising clinical studies for the treatment of haematological disorders with guadecitabine, and azacitadine plus vorinostat. He begins with a preliminary report on an ongoing phase II, single arm trial of guadecitabine against myelodysplastic syndrome and chronic myelomonocytic leukaemia, in which he notes high levels of response and low-grade toxicity, and introduces multi-centre studies also recruiting patients. Dr Montalbán Bravo also discusses azacitadine combined with vorinostat as a treatment for patients with poor performance status, and that a majority of those treated experienced a prolonged survival past the median of 60 days.

Dr Neelapu speaks with ecancertv at ASH 2016 about interim results from a phase II multicenter trial of KTE-C19 (anti-CD19 CAR T Cells) in patients with chemorefractory primary mediastinal B-Cell lymphoma (PMBCL) and transformed follicular lymphoma (TFL)

Prof Garcia-Manero speaks with ecancertv at ASH 2016 about the value of including patients in clinical trials who would be otherwise deselected based on potentially unrelated criteria. He questions the barriers to enrollment of patients, quoting exploratory 'anti-trials' of patients with confounding mental illness whose clinical utility and treatment response was equal to 'fit' participants. Prof Garcia-Manero hopes that the dogma of patient recruitment might be broached further with regulatory bodies, offering valuable learning opportunities to clinicians, and therapeutic options to otherwise discounted patients.

Dr Ravandi speaks with ecancertv at ASH 2016 with updates from the VALOR trial of vosaroxin versus placebo in combination with cytarabine. These results, first reported at ASH 2014, position vosaroxin as a major step forward for elderly patients with relapsed or refractory acute myeloid leukaemia based on its subversion of known resistance pathways.

Dr Ravandi talks to ecancertv about his highlights of ASH 2016. He discusses his interest in acute myeloid leukaemia (AML), leukaemogenesis, the use of monoclonal antibody-based therapies, ALL, CLL, minimal residual disease monitoring and where he sees research heading in the future.

Dr Jaffray speaks with ecancertv at ASH 2016 about the respective risks to patients fitted with central venous catheters as PICC lines, or tunnelling lines. She describes the risk of thrombosis over time depending on device, and the considers the likelihood of infection in long-term treatment sites. With this as the first prospective study of its kind, Dr Jaffray outlines future avenues of research, including vein specificity and expanding cohorts to infants under 6 months, and young adults.

Dr Wang meets with ecancer at ASH 2016 to discuss crenolanib, a type I FLT3 TKI inhibitor, that can be safely combined with cytarabine and anthracycline induction chemotherapy. This results in high response rates in patients with newly diagnosed FLT3 mutant acute myeloid leukaemia (AML).

Dr Pardee speaks with ecancertv at ASH 2016 about CPI-613, a novel agent which inhibits the citric acid cycle (TCA). He describes how blocking metabolic pathways with CPI-613 starves leukaemia cells of energy and reduces treatment resistance, especially when combined with cytarabine (ara-c) for older patients with relapse acute myeloid leukaemia. Dr Pardee summarises RNA-seq analysis of patient bone marrow as highlighting a possible gene signature of best responders.

Dr Mazzarella meets with ecancer at ASH 2016 to discuss his personal highlights from the conference, with special focus on improved understanding of the biologic factors and diagnostic utility in treating myeloid leukaemias. Next-generation sequencing in clinical analysis of blood cancers was reported by the group led by Dr Torsten Haferlach in the most recent issue of Blood. Dr Mazzerella considers how persistence of mutated cells might lead to relapse, to resistance and how randomised trials will shore up these initial investigations into disease clonotypes.

Dr Lamar speaks with ecancertv at ASH 2016 about phase I dose escalation of CPI-613, a metabolic inhibitor, in combination with bendamustine. She summarises the incidence and outlook of refractory T cell non-Hodgkin lymphoma (NHL), and the escalation of a small patient subgroup from 2000mg/m2, limited by toxicity. The overall response rate was 80%, and Dr Lamar describes these initial results as signs of an important crack in the armour of T cell lymphoma.

Prof Daver joins ecancertv at ASH 2016 to discuss preliminary outcomes of immunochemotherapy targeting the PD-1 checkpoint in the treatment of AML. He describes the therapy, combining standard doses of azacitadine and nivolumab, as having the potential to deliver durable complete remissions, even in relapsed patients, though does note immune toxicity in some organs. Overall, there is a significant improvement in overall survival for salvage patients, with greatest response from patients with high CD8 T cell presence. Prof Daver considers how the use of PD-1 therapies in haematological malignancies differs from solid tumours, and future avenues for immunotherapy in leukaemia treatments.

Dr Churchman speaks with ecancertv at ASH 2016 about the mutations in IKZF1, or Ikaros, that are associated with worse outcomes for childhood leukaemia. She outlines a suite of heritable mutations which result in a stem-like behaviour, cell adhesion and drug resistance within the bone marrow. Dr Churchman explains how next generation sequencing could help in identifying patients most suited to targeted therapy.

Dr Martinelli speaks with ecancertv at ASH 2016 to give his highlights from the conference. Overall, he describes research presented at this years conference as among the most invigorating in haemato-oncology after many years of incremental gains.

Prof Mateos talks to ecancer at ASH 2016 to discuss the efficacy of daratumumab, bortezomib, and dexamethasone (DVd) versus bortezomib and dexamethasone (Vd) in relapsed or refractory myeloma (RRMM), based on prior lines of therapy. The data represents an update to the CASTOR study (Palumbo A. N Engl J Med 2016). The treatment benefit of DVd vs Vd was maintained across 1 to 3 prior and 1 prior line patients. Responses for DVd were deep and durable and correlated with significantly improved outcomes versus Vd. Despite small group sizes, treatment benefit of DVd vs Vd was also observed in high-risk cytogenetic pts receiving 1-3 PL. These data continue to support the addition of daratumumab to a standard-of-care regimen in RRMM.

Prof Le Gouill speaks with ecancertv at ASH 2016 about the outcomes of the LYMA trial in France and Belgium, in which rituximab was assessed as part of maintenance therapy for young mantle cell lymphoma patients. He describes the addition of rituximab as worthy of being a new standard of care in this setting, with extensions to patient EFS, PFS and overall survival.

Prof Stilgenbauer (University of Ulm, Ulm, Germany) chairs an expert discussion for ecancertv on the latest data presented at ASH 2016 helping to shape the rapidly evolving CLL landscape. He is joined by Dr Jones (Ohio State University, Columbus, USA), Prof Wendtner (Klinikum Schwabing, Munich, Germany) and Prof Coutre (Stanford University School of Medicine, Stanford, USA). The panel first looked at presentations focused on Lenalidomide (LEN) in the maintenance setting, with results of the M1 trial of the German CLL study group showing LEN substantially prolonged PFS in high risk CLL patients as a maintenance option after chemoimmunotherapy. Although positive results were seen, it was suggested that question marks remain over the clinical utility of this treatment option. At ‘the forefront of chemo free treatments’ is ibrutinib, with follow-up data discussed from the Phase III RESONATE-2 trial, which led to the approval of ibrutinib as a first-line treatment for patients with CLL earlier in the year. Following this, the panel discussed efficacy and safety results from the longest follow-up to date for ibrutinib treated CLL/SLL patients, showing durable responses through five years of treatment. There were also positive results seen with Idelalisib in combination with Bendamustine and Rituximab in patients with Relapsed/Refractory CLL. Following previous reports of improved PFS, data presented at this year’s ASH also showed OS improvement across risk categories. Discussion then moved on to data looking at novel agents and combinations including venetoclax (VEN) monotherapy and in combination with obinutuzmab and ibrutinib. The panel also touched on results from the Phase II CLL2-BIG trial of Bendamustine followed by GA101 and Ibrutinib followed by Ibrutinib and GA101 maintenance in CLL patients. With the recent paradigm shifts in how CLL is treated, the introduction of novel agents and combinations seek to further ‘expand the CLL toolbox’. With the immunotherapy ‘hype not over’ and the role of CAR T-cell therapies being further explored, advances in CLL are set to remain the pacemaker in haematology.

Prof Lancet speaks with ecancertv at ASH 2016 about CPX-351, a liposomal delivery of cytarabine and daunorubicin, for elderly patients with advanced AML. Compared to the 7 3 schedule, he describes this subgroup as achieving better outcomes with acceptable toxicity profiles, and considers how CPX-351 might come to be used in other patient subgroups based on these results.

Prof Lancet presents at ASH 2016 to discuss CPX-351, a liposomal delivery of cytarabine and daunorubicin, for elderly patients with advanced AML following HSCT.

Prof Mhairi Copland speaks with ecancertv at ASH 2016 from the DESTINY study, a UK assessment of safely reducing dosage of tyrosine kinase therapy for patients with a deep molecular response. She describes the rationale behind the destiny study, based on TKIs most commonly prescribed to treat CML, and considers the patient benefits associated with dose reduction, including better outlooks on adverse events and affordability.

Dr Sekeres speaks with ecancertv at ASH 2016 to discuss three presentations from a press conference he chaired at the conference.

Dr Chang speaks with ecancertv at ASH 2016 about the benefits of bortezomib in the CVAD treatment schema for mantle cell lymphoma patients. She notes that, after an 8 year period, half of patients treated with VcR-CVAD remained in remission, and considers the value of bortezomib addition against the duration of treatment. Overall, Dr Chang describes this as a suitable treatment for intermediate risk patients.

Dr Shah speaks with ecancertv at ASH 2016 about the first-in-human anti-CD22 CAR T-cell therapy. She describes how therapies targetting CD19 results in diminished expression in many patients, opening the course of treatment for relapsed patients to novel targets, and that CD22 is a ubiquitous ligand with clinical utility. Based on the results from this patient group, Dr Shah considers future therapies with bi-specific T cells aimed at both CD19 and CD22 for maximum impact.

Dr Fry presents at ASH 2016 with results from the first-in-human anti-CD22 CAR T-cell therapy.

Dr Jaffray presents data at ASH 2016 on the respective risks to patients fitted with central venous catheters as PICC lines, or tunnelling lines. She describes the risk of thrombosis over time depending on device, and the considers the likelihood of infection in long-term treatment sites. With this as the first prospective study of its kind, Dr Jaffray outlines future avenues of research, including vein specificity.

Prof Mhairi Copland presents data at ASH 2016 from the DESTINY study, a UK assessment of safely reducing dosage of tyrosine kinase therapy for patients with a deep molecular response.

Prof Erba speaks with ecancertv at ASH 2016 about phase 1b trials of combining standard chemotherapy with a CD33 antibody-drug conjugate against acute myeloid leukaemia. He describes the drug design, patient characteristics and response rates, including adverse events with a tendency towards low-grade nausea and diarrhoea, and considers the significant benefits to patient outcomes after a single round of treatment.

Dr Woyach speaks with ecancertv at ASH 2016 about outcomes from RESONATE 1 2, finding ibrutinib suitable for patients of all ages, and how to treat when ibrutinib fails. She discusses age-related toxicity and discontinuation of ibrutinib, especially in older and treatment naive patients, and introduces a CD19 antibody called MOR208 for patients with ibrutinib resistance mutations. Dr Woyach considers the mutational drivers behind resistance, detectable in blood samples ahead of relapse, and how this might be a stage for pre-emptive intervention.

Dr Mahon presents data at ASH 2016 with an update from the EURO-SKI trial of TKI cessation for myeloid leukaemia patients.

Prof Erba presents results at ASH 2016 from a phase 1b study of vadastuximab talirine, or 33A, administered alongside standard induction therapy for acute myeloid leukaemia.

Dr Mahon presents data at ASH 2016 with an update from the EURO-SKI trial of TKI cessation for myeloid leukaemia patients.

Prof Keating speaks with ecancertv at ASH 2016 about presentations from Dr Terry Fry and Dr Jeff Lancet, in which twists on existing leukaemia therapies gave new insight on disease treatment

Dr Roe speaks with ecancertv at ASH 2016 about genotyping and treatment outcomes for patients with myelodysplastic syndrome with T cell large granular lymphocyte proliferations (LGL). She describes characterisation of patients by age and risk, with a greater response to lenalidomide from patients without LGL clonal types.

Dr Mascarenhas speaks with ecancertv at ASH 2016 about pacritinib, an oral kinase inhibitor against JAK2, FLT3, IRAK1, and CSF1R. He describes the patient response to pacritinib, with a direct comparison to ruxolitinib (a JAK1/2 inhibitor) being of significant interest, and weighs measuring spleen volume reduction against other endpoints. Pacritinib is currently on full clinical hold by the FDA following deaths and cardiac events in PERSIST-1, which Dr Mascarenhas considers against the toxicity profile in this trial.