SEATTLE — Nov. 18, 2021 — How to resolve disparities in access to CAR T-cell therapies? What’s the latest on new targets for CAR T cells? And what’s the link between bone marrow transplants and COVID-19?
These are a few of the questions Fred Hutchinson Cancer Research Center researchers will answer when they present the latest findings on transplantation, cell therapies, precision medicine and more at the 63rd Annual Meeting and Exposition of the American Society of Hematology (ASH).
Once known as the “Blood Club,” ASH is the world’s largest professional society serving clinicians and scientists worldwide who are working to conquer blood diseases. This year's annual meeting will highlight the latest scientific developments in hematology and will be held in person and virtually at the Georgia World Congress Center in Atlanta Dec. 11-14. An estimated 25,000 hematology professionals from 110 countries are expected to participate, along with 250 exhibitors and 200 media outlets.
Here are brief summaries of some of the research to be presented by Fred Hutch researchers. A comprehensive list is available on our ASH page, and journalists are invited to follow us on Twitter #ASH21.
For more information on any of the following presentations and to arrange interviews, please contact Molly McElroy: firstname.lastname@example.org, 206.941.8146.
CLINICAL TRIALS: CAR T-CELL THERAPY
Hutch scientists will report updates on a CD20 blood cancer target, new CAR T-cell therapies for multiple myeloma, early promise of a drug that manages severe CAR T-cell therapy side effects, and efforts to reduce disparities in access to therapy.
Poster Presentation: Safety and Efficacy of Third Generation CD20 Targeted CAR-T (MB-106) for Treatment of Relapsed/Refractory B-NHL and CLL
Abstract No. 3872
Presenter: Mazyar Shadman
Mon. Dec. 13, 6 p.m.
Currently, the FDA-approved CAR T-cell therapies for lymphoid cancers target a cancer-specific protein marker called CD19. Another CAR T-cell therapy that targets a different antigen — the CD20 protein — on cancer cells is being developed by Fred Hutch scientists in collaboration with Mustang Bio. Dr. Mazyar Shadman will give an update on the trial, which is being conducted at the Hutch’s clinical-care partner, Seattle Cancer Care Alliance. Mustang Bio expects to start accruing patients soon to a new multicenter Phase 1/2 trial under its IND, and Fred Hutch will be the lead center for that trial. More in Mustang Bio’s press release.
Dr. Mazyar Shadman: @mshadman
Oral Presentation: Safety and Efficacy of Fully Human BCMA CAR T Cells in Combination with a Gamma Secretase Inhibitor to Increase BCMA Surface Expression in Patients with Relapsed or Refractory Multiple Myeloma
Abstract No. 551
Presenter: Andrew Cowan
Sun. Dec. 12, 4:30 p.m.
Fred Hutch scientists are developing a novel immunotherapy approach for multiple myeloma, which involves a CAR T cell that targets BCMA proteins on multiple myeloma cells, plus a drug called a gamma secretase inhibitor, which increases the BCMA target on cancer cells. In an oral presentation, Dr. Andrew Cowan will give an update on the trial, which as of March 21 had treated 18 patients and found that “the combination of BCMA CAR T and GSI may augment anti-tumor activity, even when very low doses of BCMA CAR T cells are administered.” Learn more about the combination approach in this Fred Hutch news story.
Dr. Andrew Cowan: @andrewcowanmd
Poster Presentation: Safety and Efficacy of Two Anakinra Dose Regimens for Refractory CRS or Icans after CAR T-Cell Therapy
Abstract No. 2816
Presenter: Nicolas Gazeau
Sun. Dec. 12, 6 p.m.
CAR T-cell therapy has been successful in treating blood cancers, but it remains associated with significant toxicities, including cytokine release syndrome (CRS) and neurotoxicity (ICANS). Dr. Nicolas Gazeau from Fred Hutch will present on an international collaboration examining the safety and efficacy of a new way to manage those toxicities. CRS and neurotoxicity following CAR-T cells infusion are partly caused by a cytokine called IL-1. The approach works by blocking the link between IL-1 and its receptor, using an IL-1 receptor antagonist.
Dr. Nicolas Gazeau: @NGazeau14
Abstract No. 339
Presenter: Anurekha G. Hall
Dec. 11, 4:30 p.m.
“Although CAR T cells have revolutionized the treatment of relapsed B-ALL, there can be unique challenges in accessing CAR T cells,” said Dr. Anurekha Hall, a pediatric oncologist and Fred Hutch researcher. “CAR T cells are often only available at specialized centers, and for many patients this can require travel and relocation, potentially widening already existing disparities.” In a multicenter cohort of pediatric and young adult patients with B-ALL, Fred Hutch researchers found that when compared to patients who were treated locally at their own institutions, patients who were referred from an outside institution for CAR T-cell therapy were disproportionately non-Hispanic white and English-speaking. This suggests that barriers to access, such as distance and need for travel, may differentially impact Hispanic/Latino patients. Given that Hispanic/Latino patients and patients from impoverished backgrounds are known to be more likely to relapse, it is important that researchers determine how they can equitably offer CAR T-cell therapy to all patients who need them.
UPDATES ON PHASE 3 CD19 CAR T CELL TRIALS
Fred Hutch CAR T-cell therapy clinicians are looking forward to updates from Phase 3 trials on two CD19 immunotherapies on the market, liso-cel and axi-cel. Fred Hutch was part of the multisite clinical trial for liso-cel, and its scientists contributed to the design of that CAR.
PRECLINICAL THERAPEUTIC DEVELOPMENT
These presentations highlight preclinical developments in CAR T-cell therapies that Fred Hutch aims to translate toward the clinic with the help of industry partners.
Poster Presentation: Project Stella: Development and Preclinical Assessment of FOLR1-Directed Chimeric Antigen Receptor T Cells in CBF2AT3-GLIS2/RAM AML
Abstract No. 2788
Presenter: Quy Le
Sun. Dec. 12, 6 p.m.
Fred Hutch physician-scientist Dr. Soheil Meshinchi, an expert in precision medicine for acute myeloid leukemia in children and young adults, is now developing immunotherapies targeting the disease. Researchers in his lab have developed a highly specific CAR T cell targeting a rare but highly aggressive type of AML that is only seen in infants with a unique immunophenotype. The disease is highly refractory to conventional chemotherapy and other treatments. Fred Hutch clinical researcher Dr. Quy Le said this study shows that the specialized CAR T-cell therapy provides a promising treatment approach. The CAR T technology is now being transitioned to clinical development.
Poster Presentation: Targeting the Membrane-Proximal C2-Set Domain of CD33 for Improved CD33-Directed CAR T Cell Therapy
Abstract No. 2776
Presenter: Salvatore Fiorenza
Sun. Dec. 12, 6 p.m.
CAR T cells are revolutionary in treating cancer but could be even better. Knowing that the closer T cells are to cancer cells, the better they kill, Fred Hutch researchers have designed CAR T cells that bind closely to the tumor cells of a common and often fatal blood cancer — acute myeloid leukemia (AML). The reengineering works by changing the site where traditional CAR T cells bind to target cells. Using both test tube models and preclinical animal models of AML, they have shown that this new set of CAR T cells demonstrates double the killing capacity of existing CAR T cells for AML currently in clinical trials. Researchers envision other uses of the technology, including antibodies, and are now looking for an industry partner to develop the work toward a clinical trial.
Fred Hutch is known for its expertise in using the immune system to fight cancers, starting in the 1970s with the Hutch’s groundbreaking work in bone marrow transplantation. Those efforts led to a Nobel Prize in 1990.
At ASH 2021, Fred Hutch clinicians and scientists working with Dr. Geoffrey Hill, scientific director of the Immunotherapy Integrated Research Center and who holds the José Carreras/E. Donnall Thomas Endowed Chair for Cancer Research at Fred Hutch, will make several presentations on advances in transplantation, including how the microbiome influences the side effect graft-vs.-host disease.
Also, a team led by Dr. Keith Loeb will report on their project of how donor cells can end up in the brain following transplantation, and how that could be a pathway for treating neurodegenerative disorders.
Oral Presentation: The Combination of Anti-Tigit and Lenalidomide Promotes Synergistic Myeloma-Specific Immunity after ASCT
Abstract No. 328
Presenter: Simone Minnie
Sat. Dec. 11, 4 p.m.
In this session, Fred Hutch researcher Dr. Simone Minnie will discuss the ability of a new checkpoint inhibitor to TIGIT to synergize with lenalidomide to generate myeloma-specific immunity after transplant. Dr. Hill said it is exciting to see this therapeutic approach — which could have a significant clinical impact — develop, and a clinical study is planned. Learn more about this strategy in a related Fred Hutch story.
Oral Presentation: Non-Genetic Determinants of Clonotypic T Cell Expansion Following Allogeneic Stem Cell Transplant
Abstract No. 646
Presenter: Albert Yeh
Mon. Dec. 13, 10:30 a.m.
This study, presented by Fred Hutch clinical researcher Dr. Albert Yeh, suggests that microbiota help determine donor T-cell selection and expansion after bone marrow transplant. “This is important and likely to translate into clinical practice because it suggests that donor T-cell selection during graft-vs.-host disease is not all determined by genetic differences in the donor and recipient, as we previously thought,” Dr. Hill said. “This helps to direct focus on microbiota determinants of GVHD in patients, as well as donor selection, to improve transplant outcomes.”
Oral Presentation: Early Cytomegalovirus Reactivation after Allogenic Bone Marrow Transplantation Is Associated with the Loss of Recipient-Derived Humoral Immunity and Is Reduced By IL-6 Inhibition
Abstract No. 648
Presenter: Ping Zhang
Mon. Dec. 13, 10:30 a.m.
Early cytomegalovirus reactivation following allogenic bone marrow transplantation is a common and life-threatening complication. Fred Hutch researchers for years have studied both the impact of interleukin-6 on CMV development and the blockade of the IL-6 receptor as an interventional strategy. In this session, Hutch clinical researcher Dr. Ping Zhang will present new findings, from a preclinical murine model, that elucidate mechanisms involved in IL-6 inhibition. Correlating their findings with data from recent clinical trials, the researchers demonstrate the ability of IL-6 receptor blockade to maintain protective humoral responses until effective donor-derived adaptive immunity can be generated.
Oral Presentation: Donor Bone Marrow Derived Macrophage Engraftment into the Central Nervous System of Allogeneic Transplant Patients
Abstract No. 645
Presenter: Keith Loeb
Mon. Dec. 13, 10:30 a.m.
Dr. Keith Loeb will present Fred Hutch research documenting the number of donor-derived cells in the brain in 23 post-transplant brain samples — determining the effect that pre-transplant conditioning has on the number of donor-derived cells that engraft into the central nervous system. Loeb said the project, which presented many technical hurdles, will provide the basis for future cellular and gene therapy studies focused on neurodegenerative disorders, lysosomal storage diseases and autism spectrum disorders. “There are many preclinical animal models that have identified and characterized donor-derived cells in the brain, and there are a few studies showing significant therapeutic efficacy in specific disease models,” Loeb said. “The Fred Hutch studies show that a similar number of donor cells engraft into the brain of post-transplant patients effects occur in humans and should facilitate the use of hematopoietic stem cell therapy to target these diseases through microglia replacement therapy.”
Poster Presentation: COVID-19 in Pediatric Hematopoietic Cell Transplant Recipients: A CIBMTR Study
Abstract No. 2868
Presenter: Neel Bhatt
Sun. Dec. 12, 6 p.m.
Dr. Neel Bhatt, a pediatric hematologist-oncologist, will discuss his analysis of 167 pediatric hematopoietic cell transplant recipients who were diagnosed with COVID-19 post-transplant and were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). In this largest international series to date, he found that patients with pre-transplant comorbidities were more likely to develop COVID-19 and that the overall disease severity and death from COVID-19 were low in this group of patients. See a recent Fred Hutch Q&A with Dr. Bhatt on what transplant recipients and their families should keep in mind when considering returning to in-person school after transplantation during the COVID-19 pandemic.
Dr. Neel Bhatt @nbhattmd
ON THE HORIZON / OTHER ABSTRACTS
Other notable topics at ASH:
Abstract No. 2933
Presenter: Stefan Radtke
Sun. Dec. 12, 6 p.m.
Featured in the ASH Poster Walk on Emerging Research in Immunotherapies, Dec. 16, 5-6 p.m.
Gene therapy for the treatment of blood diseases/disorders is currently performed outside the patient’s body. This requires specialized facilities, which are expensive and limit gene therapy to very few locations worldwide. To enhance the feasibility and availability of gene therapy, Fred Hutch researchers evaluated polymeric nanoparticles for the delivery of gene therapy reagents. They show that polymeric nanoparticles can efficiently deliver mRNA as well as CRISPR reagents into human blood stem cells. “Most importantly, the efficiency of delivery was predictable, and loaded particles could be preserved for later use,” said Dr. Stefan Radtke, staff scientist at Fred Hutch. “In summary, polymeric nanoparticles are inexpensive, portable, and in the future can be used directly in the patient with a simple injection into the arm.”
Abstract No. 518
Presenter: Scott Furlan
Sun. Dec. 12, 4:30 p.m.
Detection of residual disease is a critical component of modern, risk-adapted therapy for acute myeloid leukemia (AML). However, the genetic and phenotypic diversity of AML has made the development of a universal assay for disease assessment particularly challenging. Fred Hutch researchers developed a platform using droplet-partitioned single-cell RNA sequencing accompanied by a computational pipeline specifically tailored to quantify residual disease after allogeneic HCT. This study demonstrated the feasibility of real-time single-cell sequencing for clinical utility. It is possible to process, capture, and sequence a patient’s sample in approximately three working days. “I believe single-cell genomics will be critical for residual disease determination in AML, especially in the post-transplant setting,” said Dr. Scott Furlan, assistant professor at Fred Hutch.
Note: Scientists at Fred Hutch played a role in developing these discoveries, and Fred Hutch and certain of its scientists may benefit financially from this work in the future. See links above to ASH abstracts for more details on individual researchers’ disclosures.
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At Fred Hutchinson Cancer Research Center, home to three Nobel laureates, interdisciplinary teams of world-renowned scientists seek new and innovative ways to prevent, diagnose and treat cancer, HIV/AIDS and other life-threatening diseases. Fred Hutch’s pioneering work in bone marrow transplantation led to the development of immunotherapy, which harnesses the power of the immune system to treat cancer. An independent, nonprofit research institute based in Seattle, Fred Hutch houses the nation’s first National Cancer Institute-funded cancer prevention research program, as well as the clinical coordinating center of the Women’s Health Initiative and the international headquarters of the HIV Vaccine Trials Network and the COVID-19 Prevention Network.