VJHemOnc Podcast

Focus on MRD: current landscape and future questions in hemonc

Measurable residual disease (MRD) has been a hot topic of interest due to its potential applications in the clinical setting. MRD measurement can help determine treatment efficacy, disease prognosis and guide disease management. In this podcast, Bijal Shah of the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Richard Dillon from King’s College London, Todd Druley of Washington University School of Medicine in St. Louis and Ola Landgren of Memorial Sloan Kettering Cancer Center explore the exciting realm of MRD.

The role of MRD as a prognostic factor, the novel technologies that can be used to detect MRD, the next steps in utilizing this measure and MRD measurement as a strategy for treatment-free survival are among the stimulating areas considered. This footage was recorded at the International Workshop on Acute Leukemias (iwAL) 2018, the British Society for Haematology (BSH) 2018 Annual Meeting, the American Society for Hematology (ASH) Annual Meeting and Exposition 2016 and 2017, and the European Hematology Association (EHA) Congress 2018.

Acute leukemias discussion: what does genomics and epigenomics tell us about patient management?

A stimulating session on the implications of genomic data for the management of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients was hosted at the 1st International Workshop on Acute Leukemias (iwAL 2018), held in St. Pete Beach, FL. Here, the session speakers discuss the intriguing presentations from the session. Mark Levis, MD, PhD, of the Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, is joined by Ari Melnick, MD, of Weill Cornell Medicine, New York, NY, Klaus Metzeler, MD, of LMU-University Hospital Munich, Munich, Germany, and Torsten Haferlach, MD, of the MLL Munich Leukemia Laboratory, Munich, Germany. Firstly, the epigenome is discussed, with the fascinating topic of epigenetic alleles covered. The clinical implications of the genetic and molecular characterization of acute leukemia are then considered. The use of artificial intelligence in the analysis of the massive amounts of data that come from genetic and epigenetic sequencing is discussed by the experts. The intriguing nature of pre-leukemic clones, which are distinct from minimal residual disease, is also explored by the panel.

Acute leukemias: is MRD already a surrogate for survival?

The use of minimal residual disease (MRD) in the management of acute leukemias is a hotly debated topic. Despite the potential of MRD status as a prognostic marker and measure of disease, there are a number of controversies surrounding its use. These were discussed in a thought-provoking session at the 1st International Workshop on Acute Leukemias (iwAL), held in St. Pete Beach, FL. Chairing the discussion, Farhad Ravandi, MD, of the University of Texas MD Anderson Cancer Center, Houston, TX, is joined by Marion Subklewe, MD, of LMU-University Hospital Munich, Munich, Germany, and Adriano Venditti, MD, University of Rome Tor Vergata, Rome, Italy. Dr Subklewe covers the use of MRD in acute myeloid leukemia (AML), which is lagging behind that in acute lymphoblastic leukemia (ALL).

A pioneer in the early use of flow cytometry for MRD measurement, Dr Venditti gives us his thoughts on the use of flow cytometry vs. other techniques for MRD assessment. The panel also discuss the preferred techniques for MRD measurement in the US and Europe in both AML and ALL. The possibility of combining flow cytometry and next-generation sequencing for MRD assessment is then explored by the experts, with strong points made for both techniques in terms of limitations and strengths. The group finally turn to the question of eradicating MRD; how useful is its measurement if we cannot combat what we discover? This podcast was recorded at the iwAL 2018.

 

Revolutionary immunotherapies for lymphoma

Immunotherapy has emerged in recent years as an effective novel treatment for lymphoma, with studies constantly striving to identify new molecules that could help patients. Here, Graham Collins, MA, MBBS, MRCP, FRCPath, DPhil, of Oxford University Hospitals NHS Foundation Trust, Oxford, UK, discusses the current state of lymphoma immunotherapy research, including follow-up data on the efficacy of rituximab, and information on several newer treatments, such as ADCC-activating monoclonal antibodies and antibody-drug conjugates. Dr Collins also discusses some of the most exciting data yet to be released in the field, such as that from the ECHELON-1 trial and the use of CAR T-cells in lymphoma. This feature was recorded at the 2017 National Cancer Research Institute (NCRI) Conference, held in Liverpool, UK.

Latest advances and current challenges in immunotherapies for lymphoma

In this lively discussion, Catherine Bollard, MBChB, MD, FRACP, FRCPA, from the Children’s National Health System and George Washington University, Washington, DC, chairs on the hot topic of immunotherapy in lymphoma. Joined by Stephan Ansell, MD, PhD, of the Mayo Clinic, MN, and Steve Gottschalk, MD, from Bayor College of Medicine, Houston, TX, they discuss the immunotherapy session at the 2017 International Workshop on Non-Hodgkin Lymphoma (iwNHL) in Vancouver, BC, Canada. The panel debate various topics, including toxicity and finding the best combinations for therapies, including the likes of CAR T-cells and immune checkpoint inhibitors.

The circle of CLL: from gene discovery to targeted treatment

In this exciting feature, Carlo Croce, MD, from Ohio State University, Columbus, OH, provides an overview of the history of advancements in chronic lymphocytic leukemia (CLL) research. Prof. Croce delivers insights into the discovery of the genetic mechanisms and targets of CLL, including his group’s identification of BCL2 and the role of two microRNAs in the pathogenesis of CLL. He explains the advances in CLL in terms of drug therapies that have been able to target the BCL2 gene, which have revolutionized the treatment of CLL patients. This feature was recorded at the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2017, held in New York, NY.

Debate on the use of MRD for multiple myeloma management

The highly anticipated panel discussion on the hot topic of MRD at the Myeloma 2017 meeting in Edinburgh, UK produced thought-provoking debate. In this video the main points of debate are discussed by Jeffrey Wolf, MD from the University of California, San Francisco, CA, Roger Owen, MD, MRCP, MRCPath of Leeds Teaching Hospitals NHS Trust, Leeds, UK, Bruno Paiva, PhD from the University of Navarra, Pamplona, Spain, Nina Shah, MD of UCSF Medical Center, San Francisco, CA and Joaquin Martinez-Lopez, MD, PhD from the Hospital Universitario, Madrid, Spain.

Questions asked in the discussion included: Should MRD be the primary endpoint for clinical trials? Should MRD negativity be the goal of myeloma treatment, and are we yet at the point to use it in the clinic? Where is MRD research going moving forward? Furthermore, the pros and cons of flow cytometry vs. next generation sequencing to determine MRD are discussed, as well as the quality control in this process.

Myeloma 2017 day 1 highlights: immunotherapy advances, a new MM subtype and liquid biopsies

Fantastic advances in immunotherapy, including CAR T-cells, bispecific antibodies and potential immunotherapy combinations, were presented at the Myeloma 2017 meeting in Edinburgh, UK. In this panel discussion, Keith Stewart, MB, ChB and Leif Bergsagel, MD from the Mayo Clinic, Scottsdale, AZ and Gareth Morgan, MD, FRCP, FRCPath, PhD of UAMS Myeloma Institute, Little Rock, AR discuss the highlights from day 1 of the meeting. In addition to immunotherapy updates, the potential for a similar phenomenon to double hit lymphoma occurring in multiple myeloma (MM), which would identify a distinct MM subgroup in need of different therapies, is discussed. Furthermore, the application of liquid biopsies and molecular diagnostics in the clinic to improve the management of patients with MM is deliberated. Exciting amyloidosis updates are also touched upon.

Myeloma 2017 day 2 highlights: MRD, targeted therapies and imaging advances

This is a very exciting time for multiple myeloma (MM) research, with advances in a range of areas from new endpoints, to novel therapies and imaging. In this video, an overview of these updates are given by Gareth Morgan, MD, FRCP, FRCPath, PhD of UAMS Myeloma Institute, Little Rock, AR, Nina Shah, MD of UCSF Medical Center, San Francisco, CA and Leif Bergsagel, MD from the Mayo Clinic, Scottsdale, AZ following day 2 of the Myeloma 2017 meeting in Edinburgh, UK.

The coverage of MRD at the meeting, including its impact on future clinical trial design, is discussed. The panel also discusses the promising results of study using nelfinavir and proteasome inhibitor combination therapy for MM. The use of further targeted therapies for MM, as well as their combinations, is also debated. Imaging advances for MM are covered and the future of drug screening on patients’ primary cells is postulated. Lastly, the panel discusses the consensus on the primary principles of MM treatment, which will drive advances in MM research.