Schedule and Program for the 2023 ASH Summit on Immunotherapies
The following programming corresponds to the 2023 ASH Summit on Immunotherapies for Hematologic Diseases. This schedule is preliminary and subject to change.
Thursday, March 2
Keynote Address
8:15 a.m. - 9:00 a.m.
Blue Room
Chair:
Shannon Maude, MD, PhD
University of Pennsylvania
Philadelphia, PA
Speaker:
T cell Therapies for Patients with Blood Disorders: Broadening Applicability
Catherine Bollard, MD, MBChB
Children's National Hospital
Washington, DC
Description:
Immunotherapies have transformed the treatment landscape for several malignant hematologic diseases and are emerging as promising options for non-malignant hematologic diseases.
Dr. Bollard will discuss T cell Therapies for Patients with Blood Disorders. Cell therapy performs an ever-increasing role to prevent and treat relapse in patients with blood cancers. Outside of T-cell engineering using chimeric antigen receptors and artificial T-cell receptors, T-cell therapies (especially in the BMT setting) have utilized ex vivo expanded antigen-specific T-cells targeting viral antigens and non-viral tumor-associated antigens. The application of antigen-specific T cell therapeutics post BMT is evidenced by donor lymphocyte infusion strategies, selective depletion, and ex vivo expansion of antigen-specific T cells. In this presentation the evolving history of T cell therapies for blood cancers with a specific focus predominantly on lymphomas will be discussed. An overview how antigen-specific T-cell therapy targeting virus and/or tumor associated antigens may contribute to enhanced overall survival especially in the BMT setting and how such approaches have broadening applicability in the field will be reviewed. In addition, the history and development of CD19 CAR T cells will be reviewed from the initial approval in the pediatric setting to the approvals in the NHL setting and comparing the evolving real-world data in the NHL setting to the results observed in the pivotal trials.
Session #1: The Science of Immunotherapy
9:00 a.m. - 10:45 a.m.
Blue Room
Chairs:
Antonio Risitano, MD, PhD
University of Naples
Naples, Italy
Madhav Dhodapkar, MBBS
Emory University
Atlanta, GA
Speakers:
Personalized Immune Based Strategies in Cancer
Catherine Wu, MD
Dana-Farber Cancer Institute
Boston, MA
The Future of Science of Cancer Immunotherapy
Ira Mellman, PhD
Genentech
New York, NY
Uncertain Mechanisms of Action of Successful Biologics - ATG Focus
Phillip Scheinberg, MD
Hospital A Beneficênica Portuguesa de São Paulo
São Paulo, Brazil
HMGA1 Chromatin Regulators Drive Immune Evasion in MPN Progression through Epigenetic Rewiring to Repress Networks Involved in Antigen Presentation
Joseph Kim
Johns Hopkins University School of Medicine
Baltimore, MD
Description:
This session will discuss the underlying science of immune-based therapies as they relate to both malignancies and classical hematologic disorders.
Dr. Ira Mellman will discuss our emerging understanding of how “checkpoint inhibitors” work, and how this impacts the design and implementation new immunotherapeutic approaches in hematologic and solid tumors. Checkpoint inhibitors have transformed outcomes in several cancers. However deeper understanding of how they work is critical for developing the next generation of immune-based therapies and combinations.
Dr. Catherine Wu will discuss how multiple lines of evidence have convincingly demonstrated tumor neoantigens as an important class of immunogenic tumor antigens and have motivated the development of personalized cancer neoantigen targeting approaches. Neoantigens arise from amino acid changes encoded by somatic mutations in the tumor cell and have the potential to bind to and be presented by personal human leukocyte antigen molecules. As a field, we have now successfully moved beyond the first wave proof-of-concept studies that have demonstrated the safety, feasibility, and high immunogenicity of these personalized vaccines. An imperative now is to address the challenges of discovering and optimizing the selection of antigens to target, the delivery approach, and extending this promising approach to a broader array of cancer settings.
Dr. Phillip Scheinberg will review the mechanism of action of antithymocyte globulin (ATG), including the different formulations. Despite the mechanism of action of these polyclonal sera not being fully understood, they have been quite successfully applied in marrow failure syndromes and the conditioning regimens in transplantation, both bone marrow and solid organs. There are two main commercially available formulations, horse and rabbit ATG, which differ in their potency and effects on the immune system. Their introduction as therapy started decades ago, and they remain one of the few non-chemotherapeutic lymphocytotoxic agents. Their applications in different disease scenarios will be summarized.
Session #2: Use of Immunotherapies in Clinical Practice or Trials
10:55 a.m. - 12:00 p.m.
Blue Room
Chairs:
Katy Rezvani, MD
The University of Texas MD Anderson Cancer
Houston, TX
Sarah Cooley, MD
Fate Therapeutics, Inc.
San Diego, CA
Speakers:
Chimeric Antigen Receptor (CAR) Engineering Beyond T-Cells
Dean Lee, MD, PhD
The Research Institute at Nationwide Children’s Hospital
Columbus, OH
T-Cell Engineering Beyond CAR
Aude Chapuis, MD
Fred Hutchinson Cancer Research Center
Boston, MA
Safety and Anti-Leukemic Activity of CD123-CAR T Cells in Pediatric Patients with AML: Preliminary Results from a Phase 1 Trial
Swati Naik, MBBS
St. Jude Children's Research Hospital
Memphis, TX
Description:
In the past decade, the field of cellular therapy has emerged as a powerful treatment modality for advanced cancers refractory to conventional therapy. Treatment with genetically engineered autologous or allogeneic immune cells has evolved from a promising concept to a clinical reality for many patients. The remarkable clinical success achieved by autologous chimeric antigen receptor T-cell (CAR-T) therapies for B cell malignancies demonstrated the potential for cellular therapy and gene editing to transform the standard of care not just for hematologic malignancies, but for solid tumor and other diseases.
This scientific session will focus on lessons learned from early cellular therapy trials and how they can inform the design of next-generation clinical studies. Presentations by leaders in the field will provide an opportunity for attendees to gain a deeper understanding of cell therapies beyond CAR T cells, including the application of alternative immune effector such as natural killer (NK) cells, approaches to improve T cell receptor (TCR) gene therapy, and the development of novel immune therapeutic agents such as bispecific for the treatment of classical hematologic diseases.
Dr. Dean Lee will discuss the growth in interest and progress in adoptive transfer of NK cells over the past few years, particularly given their low risk of alloreactivity, and therefore potential as an off-the-shelf therapeutic. NK cells have been much more difficult to genetically modify than T cells, but several recent advances have solved this, making genetically engineered off-the-shelf products possible.
Dr. Aude Chapuis will discuss her lab’s work on target identification, generation of high-affinity TCRs, cell process methodologies to translate these constructs into effective products for patients, clinical trial development and execution, and sophisticated high dimensional immune-monitoring to maximize the information that can be derived from each treated patient. Based on challenges encountered and lessons learned from previous adoptive T cell therapy trials, her lab is focusing on strategies that include eliciting increased tumor expression of the targeted HLA/peptides for better T cell recognition, maximizing T cell activation/proliferation/survival by engaging TCR-tethered co-stimulatory signals in CD4 and CD8 T cells. Dr. Chapuis will discuss the most recent strategies geared towards favoring localization and countering dysfunction of adoptively transferred TCR transgenic cells in vivo.
Session #3: Use of Immunotherapies in Clinical Practice or Trials (Cont’d)
1:00 p.m. - 2:30 p.m.
Blue Room
Chairs:
Katy Rezvani, MD
The University of Texas MD Anderson Cancer
Houston, TX
Sarah Cooley, MD
Fate Therapeutics, Inc.
San Diego, CA
Speakers:
Bispecific Antibodies in Hemophilia
Stacy Croteau, MD
Children's Hospital Boston
Boston, MA
Presentation from the Chinese Society of Hematology: BCMA CART in China and Beyond
Chengcheng Fu, MD, PhD
The First Affilliated Hospital of Soochow University
Suzhou, CHN
Tgfß-Imprinting of Primary NK Cells Decreases CD38-Nadase, Promotes a Tissue-Resident Addressin Profile, and Improves Cytotoxicity and Metabolism
Marcelo Pereira, PhD
Nationwide Children’s Hospital
Columbus, OH
Description:
In the past decade, the field of cellular therapy has emerged as a powerful treatment modality for advanced cancers refractory to conventional therapy. Treatment with genetically engineered autologous or allogeneic immune cells has evolved from a promising concept to a clinical reality for many patients. The remarkable clinical success achieved by autologous chimeric antigen receptor T-cell (CAR-T) therapies for B cell malignancies demonstrated the potential for cellular therapy and gene editing to transform the standard of care not just for hematologic malignancies, but for solid tumor and other diseases.
This scientific session will focus on lessons learned from early cellular therapy trials and how they can inform the design of next-generation clinical studies. Presentations by leaders in the field will provide an opportunity for attendees to gain a deeper understanding of cell therapies beyond CAR T cells, including the application of alternative immune effector such as natural killer (NK) cells, approaches to improve T cell receptor (TCR) gene therapy, and the development of novel immune therapeutic agents such as bispecific for the treatment of classical hematologic diseases.
Dr. Stacy Croteau will present on the use of the novel therapeutic approach of substitution therapy for hemophilia prophylaxis, namely bispecific antibody technology. Therapeutic development and clinical implications of both licensed and investigational therapies in this category will be discussed.
Session #4: Mechanisms of Resistance to Immunotherapies
2:30 p.m. - 4:15 p.m.
Blue Room
Chairs:
Rodrigo Calado, MD, PhD
University of Sao Paulo
Sao Paulo, Brazil
Loretta Nastoupil, MD
The University of Texas MD Anderson Cancer Center
Houston, TX
Speakers:
Initial Treatment Failure
Robbie Majzner, MD
Stanford University
Stanford, CA
Relapse Associated with Late Immunotherapy Failure
Nirali Shah, MD
National Cancer Institute
Bethesda, MD
Targeting Innate Immunity: Anti-Complement Therapies
Eleni Gavriilaki, MD, PhD
George Papanicolaou General Hospital
Thessaloniki, Greece
Rhoa Inactivation As a Driver of CAR-T Therapy Resistance in Diffuse Large B-Cell Lymphoma
Austin D. Newsam, BS
Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine
Miami, FL
Description:
This session will discuss cellular and molecular mechanisms involved in resistance and relapse associated with immunotherapies, including processes related to the immune system and intrinsic to the target cells. Presenters also will debate how to clinically identify resistance and strategies to overcome treatment failure.
Dr. Robbie Majzner will kick off the session discussing mechanisms of initial treatment failure with cellular therapies including antigen escape. Dr. Majzner’s laboratory focuses on extending the use of CAR T-cells to solid tumors. He has generated and optimized novel receptors to recognize antigens over-expressed on pediatric solid tumors and multi-specificity to optimize efficacy when the amount of target antigen density is limited.
Dr. Nirali Shah will discuss the various forms of post-CAR T-cell relapse following CAR T-cell therapy in B-acute lymphoblastic leukemia (e.g., antigen positive/negative relapse and/or with lineage switch). She will review factors that may influence risk of relapse, such as baseline leukemia cytogenetics, CAR T-cell construct and disease burden, and how these risk factors may inform the relapse immunophenotype. Lastly, given the poor outcomes for patients with post CAR T-cell relapse, Dr. Shah will discuss therapeutic approaches which could be utilized for the prevention and/or treatment of relapse to improve long-term outcomes.
Dr. Eleni Gavriilaki will focus on anti-complement therapy in the field of targeting innate immunity. Complement is an elaborate system of the innate immunity. Eculizumab, the first-in-class complement inhibitor, was approved for paroxysmal nocturnal hemoglobinuria (PNH) in 2007. Addressing some of the unmet needs in the field, a long-acting C5 inhibitor, ravulizumab, and a C3 inhibitor, pegcetacoplan have been also now approved with PNH. Along with these, novel agents such as factor B and factor D inhibitors, are under study with very promising results. In this era of several approved targeted complement therapeutics, selection of the proper drug is expected to be based on a personalized approach. Beyond PNH, complement inhibition has also shown efficacy and safety in cold agglutinin disease (CAD), primarily with the C1s inhibitor of the classical complement pathway, sutimlimab, but also with pegcetacoplan. Furthermore, C5 inhibition with eculizumab and ravulizumab, as well as inhibition of the lectin pathway with narsoplimab, are investigated in transplant-associated thrombotic microangiopathy (TA-TMA). With this revolution of next-generation complement therapeutics, additional hematologic entities, such as delayed hemolytic transfusion reaction (DHTR) or immune thrombocytopenia (ITP), might also benefit from complement inhibitors.
Session #5: Cell Manufacturing Considerations: Transitioning from Early to Late Phase Trials to Licensure
4:55 p.m. - 6:40 p.m.
Blue Room
Chairs:
Catherine Bollard, MD, MBChB
Children's National Hospital
Washington, DC
Terry Fry, MD
University of Colorado School of Medicine
Aurora, CO
Speakers:
Academia Perspective: Challenges in the Academia Setting to Take Novel Platforms into the Clinic - How Have They Approached IND Filings (Gene Editing)
Isabelle Riviere, PhD
Memorial Sloan Kettering Cancer Center
New York, NY
Industry Perspective: Challenges in the Industry Setting; Dealing with Adverse Events (from a GMP Perspective)
Gwen Binder, PhD
Cabaletta Bio
Philadelphia, PA
The Regulatory Perspective: Cell Manufacturing Considerations
Dr. Andrew Timmons, PhD
US Food and Drug Administration
White Oak, MD
Tunable Activation of CD19-CART Results in Enhanced Metabolic Activity and Cytotoxicity Against Antigen-Low Leukemia
Mehdi Benzaoui,
National Cancer Institute
Bethesda, MD
Description:
While current good manufacturing practice (GMP) requirements provide guidance for scalability, sustainability, testing, and quality assurance of cell and gene therapies, challenges remain especially when preparing these therapies for commercialization and “real world” post licensure use. This session will examine current GMP requirements and regulatory considerations for commercialization of cellular therapies from the academic to the industrial settings.
Dr. Isabelle Riviere will discuss from an academia perspective the challenges faced when taking novel platforms into the clinic. Specifically, she will provide discussion regarding how they have approached investigational new drug (IND) filings with respect to products that require viral vector engineering and gene editing.
Dr. Gwen Binder will approach the theme from an industry perspective focusing on the challenges in the industry setting and how to deal with adverse events from a GMP perspective. Since cell therapies are a living therapeutic, capable of continued growth once in the body some adverse events that occur can be modulated through changes in the manufacturing process. Therefore, Dr. Binder’s talk will summarize examples of seminal adverse events in cell therapy studies, including approaches and tools to mitigate future events.
Dr. Timmons from the US Food and Drug Administration will discuss the phase-based approach to the chemistry, manufacturing, and control (CMC) regulation of CAR T cell products. This presentation will outline the regulatory expectations for CAR T cell products at different stages of development, as well as highlight best practices for avoiding CMC issues throughout the product lifecycle.
Finally, Dr. Mehdi Benzaoui will discuss the impact of manufacturing, and specifically the potential for the T cell stimulation method to modulate the phenotype and function of chimeric antigen receptor T cells. While clinical trials using CD19 and CD22 CAR T-cells to treat patients with acute lymphocytic leukemia and B-lineage lymphomas have been impressively successful, it is of interest to note that these trials have differed in the methods used to generate the CAR T cells––as a function of the T cell selection method, media, cytokines, TCR activation protocol, and timing, amongst others. Here, Dr. Benzaoui will present data showing that CD19 CAR T-cells generated using a soluble, tunable activation platform based on DNA hybridization.
Friday, March 3
Session #6: Emerging Strategies to Overcome Current Immunotherapy Limitations
9:00 a.m. - 10:45 a.m.
Blue Room
Chairs:
David Scott, PhD
Uniformed Services University of Health Sciences
Bethesda, MD
Frederick Locke, MD
H. Lee Moffitt Cancer Center and Research Institute
Tampa, FL
Speakers:
Emicizumab and ITI: Partners or Foes
Shannon Meeks, MD, MBA
Emory University
Atlanta, GA
Improving CAR T By Promoting Intracellular and Extracellular Signaling
Marcela Maus, MD, PhD
Massachusetts General Hospital
Harvard Medical School, Boston, MA
Genome Editing for Adoptive T Cell Therapy
Chiara Bonini, MD
Ospedale San Raffaele
Milan, Italy
Evaluation of CD38KO/CD38-CAR Human Primary Natural Killer Cells Against CD38-Expressing Hematologic Malignancies
Ella C. Troy
Nationwide Children's Hospital
Columbus, OH
Description:
Current therapies for both malignant and classical hematologic disorders have shown promise, but multiple issues remain. This session will focus on addressing improvements that can be made to these therapies, and ways to overcome their weaknesses. The session will also complement previous sessions. Speakers will discuss ways to improve signal transduction for chimeric antigen receptions (CARs), how to overcome antigen loss and cytokine storm and highlight approaches for generating “off the shelf” CAR therapies. Addressing the use of pro-coagulant therapies and improving tolerogenic approaches to inhibitor production, and the debate over the necessity for tolerance will be discussed.
Dr. Marcela Maus will discuss recent findings underlying CAR T cell mechanisms, including the use of natural-ligand extracellular domains and their attendant biology, and the underlying role of cytokines like interferon gamma in mediating both toxicities and anti-tumor efficacy in different contexts. Dr. Maus will also discuss recent data in improving CAR T cell persistence and anti-tumor efficacy using novel transgene constructs to provide cytokine support and to overcome to the tumor microenvironment in solid tumors.
Dr. Shannon Meeks will discuss the role of immune tolerance induction (ITI) in the emicizumab era. The ability to prevent bleeding in hemophilia A with a non-factor product has allowed the opportunity to reassess treatment strategies in patients with inhibitors. Dr. Meeks will also discuss the current landscape for tolerance and whether emicizumab and ITI are partners or foes.
Dr. Chiara Bonini will discuss how the development of genetic engineering technologies dramatically changed the landscape of adoptive T cell therapy (ACT) for cancer, making this treatment accessible to an unprecedent number of patients and tumor types. By inserting a CAR or an exogeneous tumor reactive T cell receptor into patient’s T cells, the specificity can be precisely redirected toward selected tumor antigens. Gene disruption, targeted gene integration, and genome editing tools have further increased the range of opportunities for ACT. With selected biotechnological tools and protocols, we could potentially endow T cells with the ability to infiltrate the tumor mass, recognize relevant tumor antigens, resist the immunosuppressive signals present in the tumor microenvironment and persist as memory cells, to patrol the organism for recurrence. Dr. Bonini will discuss challenges and opportunities towards the generation of optimal T cell therapy products.
Session #7: Immunotherapy Toxicities – Prediction and Management
1:00 p.m. - 2:45 p.m.
Blue Room
Chairs:
Jae Park, MD
Memorial Sloan-Kettering Cancer
New York, NY
Rayne Rouce, MD
Clinical Care Center-Texas Children's Hospital
Houston, TX
Speakers:
Cytokine Release Syndrome
David Teachey, MD
Children's Hospital of Philadelphia
Philadelphia, PA
Neurotoxicity
Juliane Gust, MD, PhD
Seattle Children's Hospital
Seattle, WA
Off-Target Effects of Immunotherapy
Elad Sharon, MD, MPH
National Cancer Institute
Bethesda, MD
Description:
Discuss immunotherapy toxicities and management as well as emerging data on biomarkers and risk prediction models.
Dr. David Teachey will provide updates on the diagnosis and management of cytokine release syndrome (CRS). This discussion will focus on similarities and differences in clinical, laboratory, and biologic manifestations of CRS based on patient population, immunotherapy target, and disease treated. Further, risk prediction models, HLH-like toxicities and novel treatment approaches, including targeting Jak/Stat and interferon gamma blockade will be reviewed.
Dr. Juliane Gust will provide updates on risk prediction and management of immune effector cell associated neurotoxicity syndrome (ICANS). We will discuss the different clinical presentations of ICANS, the evidence base for graded monitoring and intervention approaches, and the expanded spectrum of neurologic toxicities in cell based immunotherapy.
Dr. Sharon will discuss efforts to learn more about off-target effects of immunotherapy, including efforts to collect clinical data and samples from national clinical trials, sponsored by the NCI and other academic organizations. Through efforts focused on translational science, the pathogenesis and eventual treatments for these irAEs may expand the reach of immunotherapy through better management of toxicity, as well as elucidate mechanisms behind similar cognate autoimmune syndromes that arise spontaneously. Immunotherapy is revolutionizing cancer care, primarily through the use of immune checkpoint inhibitors (ICIs) in an increasing number of histologies and settings. Unfortunately, ICIs and other immunotherapy agents have been associated with immune-related Adverse Events (irAEs), which are rare but serious sequelae of treatment with immuno-oncology therapeutics. These therapeutics include monoclonal antibody antagonists targeting programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors.
Session #8: Late Breaking Special Session (ASH-SITC JOINT Session)
2:55 p.m. - 4:10 p.m.
Blue Room
Chairs:
John Tisdale, MD
NIH Molecular & Clinical Hematology
Bethesda, MD
Nina Shah, MD
University of California San Diego
San Diego, CA
Speakers:
The Immune Predictors of Response to CAR T and Bispecific T Cell Therapy
Paola Neri, MD, PhD
University of Calgary
Calgary, Canada
Novel Technologies to Improve and Safely Deliver Gene Therapies
Jennifer E. Adair, PhD
Fred Hutchinson Cancer Center
Boston, MA
Cord Blood-Derived CD19-Specific Chimeric Antigen Receptor T Cells: An Off-the-Shelf Promising Therapeutic Option for Treatment of Diffuse Large B-Cell Lymphoma
Tiantian Yu, PhD
The Second Affiliated Hospital of Nanchang University
Nanchang, China
Description:
Dr. Paola Neri will discuss the Immune predictors of response to chimeric antigen receptor (CAR) T and bispecific T cell therapy in multiple myeloma (MM). She will start by describing the mechanisms of tumor escape that allow MM progression and development of immune dysfunction. Next, she will review the T-Cell based strategies developed to overcome immune escape with a focus on CAR-T and bispecific T cell therapy. Lastly, Dr. Neri will discuss the causes of resistance to these therapies and how a comprehensive genomic analysis of the tumor together with the study of the immune cell repertoire can help to identify patients with the highest likelihood of respond to these therapies and lead to the development of prevention strategies.