Special Scientific Symposia

These sessions will take place from Saturday through Monday and will feature transformative research with implications for scientific investigation and clinical practice across the field of hematology.

Changing the Taxonomy of Aggressive Lymphoma: Ready to Impact Clinical Management?

Sunday, December 8, 2019, 7:30 a.m. - 9:00 a.m.
Orange County Convention Center, Tangerine 2 (WF2), Level 2

In the past two decades, major advances have been made in the science of aggressive B-cell lymphoma, and diffuse large B-cell lymphoma (DLBCL) in particular. Once thought to be a single entity, it was initially found through genetic laboratory studies (mostly gene expression profiling), and the discovery of subtype-specific genetic aberrations that DLBCL could be divided into activated B-cell (ABC), germinal center B-cell (GCB), and primary mediastinal large B cell lymphoma (PMBCL) phenotypes. Accompanying these basic science findings were emerging implications for prognosis as well as treatment of these distinct subtypes. In addition, further investigations were undertaken in the laboratory as well as the clinic into less common aggressive lymphoma subtypes, to define their pathologic and genetic characteristics. This session will review these genetic-based classifications, and their potential impact on clinical care.

Dr. David Scott will review gene expression-based classifiers in aggressive B-cell lymphomas, focusing on DLBCL cell-of-origin, the distinction between PMBCL and DLBCL, and the "double hit signature" that is characteristic of cases with coexisting chromosomal rearrangements of the MYC, BCL2 and/or BCL6 oncogenes. He will further discuss the concept that gene expression summates upstream genetic aberrations and that gene expression-based assays can complement the genetics-based classifiers, with implications for clinical trials and treatment decisions.

Dr. Margaret Shipp will discuss the genetic substructure of DLBCL, with implications for diagnosis, prognosis, and therapy. She will present her data on the recurrent mutations, somatic copy number alterations, and structural variants from a large cohort of newly diagnosed DLBCL patients. Five robust DLBCL subsets were subsequently defined, including a previously unrecognized group of low-risk ABC-DLBCLs of extrafollicular/marginal zone origin, two distinct subsets of GCB-DLBCLs with different outcomes and targetable alterations, and an ABC/GCB-independent group with biallelic inactivation of TP53, CDKN2A loss, and associated genomic instability. The genetic features of these distinct DLBCL subsets will be summarized, with implications for disease pathogenesis, outcomes independent of the international prognostic index, and treatment strategies.

Dr. Megan Lim will review "gray zone lymphomas", which typically refers to a group of lymphoid neoplasms exhibiting a spectrum of morphologic, immunophenotypic and pathogenetic features, which poses challenges for reproducible diagnosis and for appropriate selection for novel pathogenetically-relevant clinical trials. Recent updates in the pathologic, genetic, and proteomic features of gray-zone lymphomas of B-lineage (with features intermediate between classic Hodgkin lymphoma, and primary mediastinal/large B-cell lymphoma; Burkitt lymphoma and high-grade B-cell lymphomas) will be discussed.

Co-Chairs:

Christian Steidl, MD
British Columbia Cancer Agency
Vancouver, Canada

Vicki A. Morrison, MD
Hennepin County Medical Center, University of Minesota
Minneapolis, MN

Speakers:

David W Scott, MBChB, PhD
British Columbia Cancer
Vancouver, BC, Canada
Gene Expression-based Classifications: Have They Finally Arrived?

Margaret A. Shipp, MD
Dana Farber Cancer Institute
Boston, MA
The Genetic Substructure of Diffuse Large B-cell Lymphoma: Implications for Diagnosis, Prognosis and Therapy

Megan S. Lim, MD,PhD
University of Pennsylvania
Philadelphia, PA
The Pathology of Grey Zone Lymphomas and Rarer Entities

Drugging the Undruggable

Saturday, December 7, 2019, 4:00 p.m. - 5:30 p.m.
Orange County Convention Center, W331, Level 3

The ground-breaking sequencing of the first leukemia genome was presented at the American Society of Hematology Meeting in 2007. Over the next decade, there has been an unprecedented increase in the application of massively parallel sequencing to the characterization of human malignancies. While advances in technologies have profoundly deepened researchers’ knowledge of these diseases, challenges still lie ahead, such as the successful translation of next-generation sequencing approaches to the actual care of patients with cancer. Moreover, a significant number of patients lack an immediately "druggable" cancer-associated genetic alteration. Often, these patients have abnormalities of transcription factors or other historically intractable therapeutic targets. This session will focus on the application of new, cutting-edge genomic and chemistry-based approaches aimed at addressing challenges during this next phase of molecularly informed cancer therapy.

Dr. David Solit will discuss recent advances in precision oncology and the application of massively parallel sequencing to patient care. In particular, he will focus on insights gained from the study of extraordinary responders and the prospective tumor/normal profiling initiative at his institution.

Dr. Kimberly Stegmaier will discuss the application of genome-scale functional genomic screens to identify new "synthetic lethal" liabilities. This will be discussed in the context of aberrant transcription factors, including transcription factor fusions, expressed in malignancies typically lacking matched targeted therapies. One alternative approach to targeting these cancers is to identify vulnerabilities incurred by the cells in the context of the oncogenic transcription factor.

Dr. Craig Crews will discuss PROTAC-mediated protein degradation, a chemical biology concept that has successfully transitioned from the laboratory to the clinic (first clinical trials began in March 2019 for prostate cancer). This new technology has great potential to increase the druggable target space. Several hematological PROTAC targets have been successfully degraded, demonstrating the feasibility of using this new modality to treat cancers, including those hematologic malignancies driven by transcription factor fusions and other difficult drug targets.

Chair:

Kimberly Stegmaier, MD
Dana-Farber Cancer Institute
Boston, MA

Speakers:

David B. Solit, MD
Memorial Sloan Kettering Cancer Center
New York, NY
Lessons from the Study of Exceptional Responders

Kimberly Stegmaier, MD
Dana-Farber Cancer Institute
Boston, MA
Finding Achilles' Heels of Fusion-driven Malignancies

Craig M. Crews, PhD
Yale University
New Haven, CT
PROTAC-mediated Protein Degradation: A New Therapeutic Modality

Lost in Translation: Overcoming Roadblocks in Translating New Therapeutics to the Clinic

Sunday, December 8, 2019, 9:30 a.m. - 11:00 a.m.
Orange County Convention Center, Valencia A (W415A), Level 4

Many hematologists/oncologists participate in the identification and development of new therapeutic approaches for hematological diseases, but they may lack knowledge or encounter barriers that impede successful clinical translation of promising technologies. In a format new to ASH, this session will be an actively moderated panel discussion using real-world examples to highlight key barriers in drug development. Two case studies will be presented, one focused on small molecule development and the other on cell therapy development, as a means of highlighting common roadblocks and challenging issues faced in the translation of experimental therapies into practice. A panel of experts drawn from academia, industry, business, and the U.S. Food and Drug Administration (FDA) will discuss these obstacles and how they might be overcome.

Dr. Andrew Roberts will discuss the development of venetoclax, a specific inhibitor of BCL2. From an academic perspective, the development of BCL2 inhibitors was complicated by both the failure in clinical trials of prior compounds putatively targeting BCL2 and by competition from big pharma. The case of venetoclax raises issues of deciding when a therapeutic target is worth pursing, how and when to partner with industry, and grappling with challenges in early clinical trials.

Dr. Colleen Delaney will discuss the development of non- human leukocyte antigen matched, ex vivo expanded cord blood cellular therapies. She will describe her path translating basic discovery to investigational new drug-enabling studies, chemistry, manufacturing, and control development and current good manufacturing practices in academia to support early clinical trials and the ultimate decision to spin this technology out of the Fred Hutchinson Cancer Research Center into a new start-up. This case study will examine lessons learned and the perceived and real hurdles faced on this path from academics to industry as well as address the decision-making that goes into beginning a biotech startup. She will examine issues related to the relationship between the academic institution and the startup and navigation of the 'valley of death' (financing in early stages when cash flow is a significant problem), among other issues faced by a biotech startup.

Dr. Gideon Bollag will provide the industry prospective on collaborating with academic institutions and highlight differences between drug development approaches in academia and industry.

Dr. Rosana Kapeller will comment on the cases presented by Drs. Delaney and Roberts from the point of view of the entrepreneur, explaining the role of the investment community in drug development and discussing what characteristics make a new therapeutic approach appealing or unattractive from the business prospective.

Dr. Ann Farrell will address the regulatory process for small molecules and cell-based therapeutics (e.g., obtaining an Investigational New Drug (IND), responding to FDA review, etc.) and will discuss common regulatory hurdles.

Co-Chairs:

Andrew W. Roberts, MBBS, PhD
Walter and Eliza Hall Institute of Medical Research
Melbourne, Australia

Colleen Delaney, MD, MSc
Nohla Therapeutics
Seattle, WA

Speakers:

Gideon Bollag, PhD
Plexxikon Inc.
Berkeley, CA
Industry Perspective

Rosana Kapeller, MD, PhD
Google Ventures
Mountain View, CA
Entrepreneur-in-Residence

Ann T. Farrell, MD
U.S. Food and Drug Administration
Bethesda, MD
U.S. Food and Drug Administration's Perspective

Machine Learning in Hematology

Saturday, December 7, 2019, 4:00 p.m. - 5:30 p.m.
Orange County Convention Center, Hall D, Level 2

The landscape of molecular and functional patient information has been rapidly expanding across all fields of medicine. There has been increasing focus on incorporating individualized patient attributes into clinical care. Multiomics data are now available, including genomics, transcriptomics, proteomics, metabolomics, and others. New bioinformatics methods for analyzing the vast and complicated wealth of information are needed. Machine Learning (ML), a component of artificial intelligence, refers to the methodology by which computer systems can analyze and interpret complex datasets in a manner that will predict outcomes or correlate with disease status. These algorithms have the potential to provide critical prognostic data, optimize precision medicine approaches, and improve accuracy and efficiency of pathologic diagnosis.

Dr. Kun-Hsing Yu will discuss how ML can integrate data generated by various modalities to enhance oncology research and practice. Recent progress in digitized data acquisition, data-driven algorithms, and computing infrastructure, have empowered ML applications for cancer subtype identification and survival outcome prediction. In this talk, he will outline recent breakthroughs in ML technologies and their applications in data integration, highlight the advances in quantitative pathology analyses, and identify the challenges for further progress in ML systems.

Dr. Pamela Becker will discuss an ML algorithm called MERGE based on genomics data to correlate gene expression with drug sensitivity in patients with acute myeloid leukemia (AML). Using MERGE, ~40 genes were identified for which high expression was correlated with sensitivity or resistance to classes of drugs in AML. Dr. Becker is also working with colleagues on deep learning methods to track the morphology, phenotype, and viability of AML cells in real time by video microscopy after drug exposure. These predictive algorithms, in combination with molecular data and functional screening, can be combined to optimize treatment for individual patients.

Dr. Lee Cooper will discuss how ML applied to digital pathology imaging enables quantitative and scalable evaluation of histology samples. In hematologic malignancies, this technology has the potential to improve diagnostic reproducibility and to optimize diagnostic criteria. His talk will discuss the development of ML algorithms for bone marrow aspirate smears and diffuse large B-cell lymphomas. In addition, he will illustrate challenges and opportunities in applying ML and address the critical role of data collection and validation in system development.

Chair:

Pamela S. Becker, MD, PhD
University of Washington
Seattle, WA

Speakers:

Kun-Hsing Yu, MD, PhD
Harvard Medical School
Boston, MA
Integrating Quantitative Pathology and Multi-Omics Profiles using Machine Learning

Pamela S. Becker, MD, PhD
University of Washington
Seattle, WA
Machine Learning for Precision Medicine in Acute Myeloid Leukemia

Lee Cooper, PhD, MS
Northwestern University Feinberg School of Medicine
Chicago, IL
Using Machine Learning to Improve Histological Diagnoses of Hematologic Malignancies

Special Symposium on the Basic Science in Hemostasis and Thrombosis

Monday, December 9, 2019, 4:30 p.m. - 6:30 p.m.
Orange County Convention Center, Tangerine 3 (WF3-4), Level 2

The Scientific Committees on Hemostasis, Thrombosis and Vascular Biology and Megakaryocytes and Platelets have developed a session focused on highlighting cutting-edge research being performed by leading investigators in the respective fields. The program will highlight new basic science advances in areas of clinical importance.

Dr. David Lillicrap will discuss the critical role two procoagulant proteins, factor VIII (FVIII) and von Willebrand factor (VWF), play in the hemostatic process. Inherited deficiency states of these proteins result in the bleeding diseases (e.g., hemophilia A and von Willebrand disease), and increased plasma levels of the proteins are significant risk factors for arterial and venous thrombosis. Aspects of the FVIII/VWF interaction will be highlighted with reference to the biology and pathobiology of hemostasis.

Dr. S. Ananth Karumanchi will discuss evidence suggesting that excess soluble fms-like tyrosine kinase1, an endogenous soluble inhibitor of VEGF signaling, may play a causal role in the pathogenesis of preeclampsia. Circulating levels of sFlt1 and placental growth factor PlGF, a ligand for sFlt1 may be used as markers for the early diagnosis of preeclampsia. He will highlight novel treatments such as therapeutic apheresis and RNA interference strategies targeting sFlt1, which are aimed at shifting the balance in favor of pro-angiogenesis and endothelial health for this syndrome.

Dr. Martha Sola-Visner will describe the growing body of evidence suggesting that neonatal megakaryopoiesis is characterized by a developmentally unique dissociation between proliferation, polyploidization and maturation, challenging the paradigm that neonatal megakaryocytes and platelets are simply “immature”. She will discuss the key differences between fetal/neonatal and adult megakaryopoiesis, and their significance in normal development, disease pathogenesis, and response to novel therapies.

Co-Chairs:

Sriram M. Krishnaswamy, PhD
Children's Hospital of Philadelphia
Philadelphia, PA

Jordan A. Shavit, MD,PhD
University of Michigan
Ann Arbor, MI

Jeffrey I. Zwicker, MD
Beth Israel Deaconess Medical Center, Harvard Medical School
Boston, MA

Saskia Middeldorp, MD, PhD
University of Amsterdam
Amsterdam, Netherlands

Speakers:

David Lillicrap, MD
Queen's University
Kingston, Canada
The FVIII/VWF Axis: Consequences of an Unequal Partnership

Subbian Ananth Karumanchi, MD
Cedars-Sinai Medical Center
Los Angeles, CA
Angiogenic Factors and Endothelial Dysfunction in Pre-eclampsia

Martha Sola-Visner, MD
Boston Children's Hospital
Boston, MA
Developmental Differences Between Neonatal and Adult Megakaryopoiesis